Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (669 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
A class of membrane lipids that have a polar head and two nonpolar tails. They are composed of one molecule of the long-chain amino alcohol sphingosine (4-sphingenine) or one of its derivatives, one molecule of a long-chain acid, a polar head alcohol and sometimes phosphoric acid in diester linkage at the polar head group. (Lehninger et al, Principles of Biochemistry, 2nd ed)
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Sphingolipid; Lysosphingolipids.
Where it fits in the MeSH classification
- Broader topics
- Membrane Lipids
- Narrower topics
- Glycosphingolipids
- See also
- Sphingosine
Research landscape
PubMed indexes 43,296 records tagged with the MeSH heading “Sphingolipids” (counts retrieved 2026-10-31). 5,955 of them (13.8%) were published from 2020 onward, and the busiest period so far is through 1999 with 18,586 records.
Reviews account for 4,505 records (10.4%) and meta-analyses for 31. Randomized controlled trials number 268 (0.6%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 18,586 |
| 2000-2009 | 9,315 |
| 2010-2019 | 9,440 |
| 2020 onward | 5,955 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 4,505 | 10.4% |
| Meta-analyses | 31 | 0.1% |
| Randomized controlled trials | 268 | 0.6% |
Method: PubMed query "Sphingolipids"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in drugs and chemicals
Studies of a chemical or drug can answer very different questions: what it is and how it behaves in cells and animals, how the body handles it, and whether it changes outcomes in people. Laboratory and animal findings often do not carry over to patients, and observational studies of exposures are confounded by who uses a substance and why. Nothing on this page is a recommendation to use, avoid, start or stop any substance or medicine; talk to a qualified clinician or pharmacist about your own situation. Check the dose, the species, the comparison group and whether a patient-relevant outcome was measured.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Microglia-neuron crosstalk through Hex-GM2-MGL2 maintains brain homeostasis | 2025 | Research article Design not recorded in structured metadata | 39 | cc by PMID 40769205 · DOI · PMC12545202 |
| The bioactive sphingolipid playbook. A primer for the uninitiated as well as sphingolipidologists | 2025 | Review article Design not recorded in structured metadata | 13 | cc by PMID 40254066 · DOI · PMC12255454 |
| Fundamental Neurochemistry Review: Sphingolipids and Ceramides in Brain Development | 2025 | Review article Design not recorded in structured metadata | 10 | cc by PMID 41121737 · DOI · PMC12541296 |
| Sphingolipids in Emotional Well-Being | 2026 | Review article Design not recorded in structured metadata | 5 | cc by PMID 41700345 · DOI · PMC12910332 |
Microglia-neuron crosstalk through Hex-GM2-MGL2 maintains brain homeostasis [1]
Abstract reading summary — source excerpts
- Opening excerpt
- As tissue-resident macrophages of the central nervous system parenchyma, microglia perform diverse essential functions during homeostasis and perturbations1.
- Closing excerpt
- Our results reveal a mode of bidirectional microglia-neuron communication centred around GM2 ganglioside turnover, identify a microgliopathy and offer therapeutic avenues for these maladies.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (195 words)
As tissue-resident macrophages of the central nervous system parenchyma, microglia perform diverse essential functions during homeostasis and perturbations1. They primarily interact with neurons by means of synaptic engulfment and through the rapid elimination of apoptotic cells and non-functional synapses2. Here, by combining unbiased lipidomics and high-resolution spatial lipid imaging, deep single-cell transcriptome analysis and novel cell-type-specific mutants, we identified a previously unknown mode of microglial interaction with neurons. During homeostasis, microglia deliver the lysosomal enzyme β-hexosaminidase to neurons for the degradation of the ganglioside GM2 that is integral to maintaining cell membrane organization and function. Absence of Hexb, encoding the β subunit of β-hexosaminidase, in both mice and patients with neurodegenerative Sandhoff disease leads to a massive accumulation of GM2 derivatives in a characteristic spatiotemporal manner3. In mice, neuronal GM2 gangliosides subsequently engage the macrophage galactose-type lectin 2 receptor on microglia through N-acetylgalactosamine residues, leading to lethal neurodegeneration. Notably, replacement of microglia with peripherally derived microglia-like cells is able to break this degenerative cycle and fully restore central nervous system homeostasis. Our results reveal a mode of bidirectional microglia-neuron communication centred around GM2 ganglioside turnover, identify a microgliopathy and offer therapeutic avenues for these maladies.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 40769205 · DOI · PMC12545202
The bioactive sphingolipid playbook. A primer for the uninitiated as well as sphingolipidologists [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Sphingolipids and glycosphingolipids are among the most structurally diverse and complex compounds in the mammalian metabolome.
- Closing excerpt
- Therefore, this review gives an overview of essential elements of sphingolipid structure and analysis, metabolism, functions, and roles in disease and discusses some of the items to consider when interpreting lipidomics data and designing follow-up investigations.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (147 words)
Sphingolipids and glycosphingolipids are among the most structurally diverse and complex compounds in the mammalian metabolome. They are well known to play important roles in biological architecture, cell-cell communication, and cellular regulation, and for many biological processes, multiple sphingolipids are involved. Thus, it is not surprising that untargeted genetic/transcriptomic/pharmacologic/metabolomic screens have uncovered changes in sphingolipids and sphingolipid genes/proteins while studying physiological and pathological processes. Consequently, with increasing frequency, both targeted and untargeted mass spectrometry methodologies are being used to conduct sphingolipidomic analyses. Interpretation of such large data sets and design of follow-up experiments can be daunting for investigators with limited expertise with sphingolipids (and sometimes even for someone well-versed in sphingolipidology). Therefore, this review gives an overview of essential elements of sphingolipid structure and analysis, metabolism, functions, and roles in disease and discusses some of the items to consider when interpreting lipidomics data and designing follow-up investigations.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 40254066 · DOI · PMC12255454
Fundamental Neurochemistry Review: Sphingolipids and Ceramides in Brain Development [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Lipids are emerging as key players in regulating neural stem cells and their progeny.
- Closing excerpt
- We further summarize the importance of ceramides in different intracellular compartments and organelles, and finally discuss the alterations of sphingolipid metabolism in neurological disorders, particularly of neurodevelopmental origin.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (107 words)
Lipids are emerging as key players in regulating neural stem cells and their progeny. Recent lipidomic profiling studies clearly illustrate the significance of lipids across cerebral cortical development and evolution. In this review, we identify the existing knowledge concerning the importance of lipids in cortex development and neurogenesis processes, with a special emphasis on ceramide-based sphingolipids. We then discuss the lipidation of factors that are relevant for cortex development and how their interaction with ceramides facilitates certain intracellular processes. We further summarize the importance of ceramides in different intracellular compartments and organelles, and finally discuss the alterations of sphingolipid metabolism in neurological disorders, particularly of neurodevelopmental origin.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41121737 · DOI · PMC12541296
Sphingolipids in Emotional Well-Being [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Emotional well-being is a multifactorial concept, which comprises not only life quality of human individuals, but also their mental and physical health.
- Closing excerpt
- SLs are suggested as a potentially new mechanism of the key behavioral manifestations of emotional well-being, which might be further investigated as new biomarkers of life quality as well as physical and mental resilience.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (220 words)
Emotional well-being is a multifactorial concept, which comprises not only life quality of human individuals, but also their mental and physical health. It encompasses several key parameters, many of which have behavioral representation in daily life. These include finding positive meaning of life events, ability to maintain supportive and caring social interactions, reward-oriented behavior, and many others. It is well-known that the behavioral phenotype is tightly bound to certain physiological and metabolic factors, among which sphingolipid (SL) balance of the organism and especially central nervous system might play an important role. Recent research proposes that SLs mediate multiple components of emotional well-being. The most abundant brain SL types, ceramides and gangliosides, dynamically shape the composition of protein carrying cellular membranes and overall neuronal plasticity. Multiple studies show the contribution of SLs to normal brain functioning and corresponding beneficial behavioral phenotypes, such as stress resilience, cognitive performance, and social interactions, which determine emotional well-being. On the other hand, an imbalance in SL metabolism affects normal functioning of cells and thus contributes to the development of several psychiatric disorders, such as depression, anxiety, cognitive decline, schizophrenia, and others. SLs are suggested as a potentially new mechanism of the key behavioral manifestations of emotional well-being, which might be further investigated as new biomarkers of life quality as well as physical and mental resilience.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41700345 · DOI · PMC12910332
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Ceramides and other sphingolipids as drivers of cardiovascular disease [5]
- Research article Role of cholesterol and sphingolipids in brain development and neurological diseases [6]
- Research article Ceramides in Metabolism: Key Lipotoxic Players [7]
- Research article Sphingolipids in metabolic disease: The good, the bad, and the unknown [8]
- Research article Metabolic Messengers: ceramides [9]
- Research article A Comprehensive Review: Sphingolipid Metabolism and Implications of Disruption in Sphingolipid Homeostasis [10]
References
- Frosch M, Shimizu T, Wogram E, Amann L, Gruber L, Groisman AI, et al.. Microglia-neuron crosstalk through Hex-GM2-MGL2 maintains brain homeostasis. . 2025. PMID 40769205 · DOI · PMC12545202
- Hannun YA, Merrill AH, Luberto C. The bioactive sphingolipid playbook. A primer for the uninitiated as well as sphingolipidologists. . 2025. PMID 40254066 · DOI · PMC12255454
- Chinnappa K, Ballorin F, Francis F. Fundamental Neurochemistry Review: Sphingolipids and Ceramides in Brain Development. . 2025. PMID 41121737 · DOI · PMC12541296
- Kalinichenko LS, Zoicas I, Mühle C, Kornhuber J, Müller CP. Sphingolipids in Emotional Well-Being. . 2026. PMID 41700345 · DOI · PMC12910332
- Choi RH, Tatum SM, Symons JD, Summers SA, Holland WL. Ceramides and other sphingolipids as drivers of cardiovascular disease. Nat Rev Cardiol. 2021. PMID 33772258 · DOI · PMC8978615
- Hussain G, Wang J, Rasul A, Anwar H, Imran A, Qasim M, et al.. Role of cholesterol and sphingolipids in brain development and neurological diseases. Lipids Health Dis. 2019. PMID 30683111 · DOI · PMC6347843
- Chaurasia B, Summers SA. Ceramides in Metabolism: Key Lipotoxic Players. Annu Rev Physiol. 2021. PMID 33158378 · DOI · PMC7905841
- Green CD, Maceyka M, Cowart LA, Spiegel S. Sphingolipids in metabolic disease: The good, the bad, and the unknown. Cell Metab. 2021. PMID 34233172 · DOI · PMC8269961
- Summers SA, Chaurasia B, Holland WL. Metabolic Messengers: ceramides. Nat Metab. 2019. PMID 32694860 · DOI · PMC7549391
- Quinville BM, Deschenes NM, Ryckman AE, Walia JS. A Comprehensive Review: Sphingolipid Metabolism and Implications of Disruption in Sphingolipid Homeostasis. Int J Mol Sci. 2021. PMID 34071409 · DOI · PMC8198874
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-31.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.