| Full Name | Ceramide Kinase |
|---|---|
| Gene Symbol | CERK |
| Chromosome | 22q13.31 |
| NCBI Gene ID | [54660](https://www.ncbi.nlm.nih.gov/gene/54660) |
| OMIM | [609250](https://omim.org/entry/609250) |
| Ensembl | [ENSG00000100324](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000100324) |
| UniProt | [Q8TCT0](https://www.uniprot.org/uniprot/Q8TCT0) |
| Encoded Protein | [CERK protein](/proteins/cerk-protein) |
| Associated Diseases | Alzheimer's disease, Stroke, Neuroinflammation, Cancer |
CERK (Ceramide Kinase) encodes the enzyme that converts ceramide to ceramide-1-phosphate (C1P), a bioactive lipid mediator involved in cell proliferation, survival, inflammation, and membrane trafficking.[1] In the nervous system, CERK-C1P signaling modulates neuronal survival, microglial activation, and neuroinflammatory responses.[2] Dysregulation of ceramide metabolism is increasingly recognized as contributing to neurodegeneration, with CERK positioned at a critical branchpoint between pro-apoptotic ceramide and pro-survival C1P signaling.
The CERK gene spans approximately 82 kb on chromosome 22q13.31 and contains 11 exons.[3] The encoded 538-amino acid protein contains:
Expression in the nervous system: CERK is expressed in neurons and glia throughout the brain, with highest expression in hippocampus, cortex, and cerebellum.[4] Expression increases in response to inflammatory stimuli and ischemic injury.
CERK catalyzes the phosphorylation of ceramide:[5]
Ceramide-1-phosphate mediates multiple cellular processes:[6]
CERK-C1P in neuroinflammatory responses:[7]
CERK determines the ceramide/C1P balance:[8]
| Pathway | Lipid | Cellular Effect |
|---|---|---|
| Ceramide accumulation | Ceramide | Apoptosis, ER stress, autophagy |
| CERK activation | C1P | Survival, proliferation, inflammation |
| Sphingomyelin hydrolysis | Ceramide | Stress response |
| C1P phosphatase | Ceramide | Reversal of C1P effects |
CERK and ceramide dysregulation in AD:[9]
CERK in cerebral ischemia:[10]
CERK in inflammatory conditions:[11]
CERK in tumor biology:[12]
| Tissue | Expression Level | Notes |
|---|---|---|
| Hippocampus | High | Memory circuits, vulnerable in AD |
| Cerebral cortex | High | Cognitive function |
| Microglia | High | Inflammatory mediator |
| Astrocytes | Moderate | Support cells |
| Oligodendrocytes | Moderate | Myelin maintenance |
| Variant | dbSNP | Effect | Clinical Relevance |
|---|---|---|---|
| rs2240246 | NCBI | Intronic | Stroke susceptibility |
| rs2070874 | NCBI | 3' UTR | Gene expression modifier |
| rs8137581 | NCBI | Intronic | Inflammatory response modifier |
Approaches targeting CERK-C1P axis:[13]
Sugiura M, et al. Ceramide kinase, the enzyme producing ceramide-1-phosphate. Biochem Biophys Res Commun. 2002. ↩︎
Olivera A, et al. Ceramide kinase and C1P in cell regulation. Adv Exp Med Biol. 2013. ↩︎
Bornancin F, et al. Molecular cloning and characterization of ceramide kinase. J Biol Chem. 2002. ↩︎
Mitsutake S, et al. CERK expression in brain tissues. Neurochem Int. 2007. ↩︎
Wijesinghe DS, et al. Substrate specificity of ceramide kinase. J Lipid Res. 2005. ↩︎
Arana L, et al. Ceramide-1-phosphate signaling in cell biology. Prog Lipid Res. 2010. ↩︎
Presa N, et al. C1P in inflammation and immune responses. Biochim Biophys Acta. 2016. ↩︎
Gault CA, et al. Ceramide and C1P balance in disease. Adv Biol Regul. 2018. ↩︎
Filippov V, et al. Ceramide metabolism in Alzheimer's disease. J Alzheimers Dis. 2012. ↩︎
Novgorodov SA, et al. C1P and neuroprotection in stroke. Mol Neurobiol. 2014. ↩︎
Van Echten-Deckert G, et al. Sphingolipids in neuroinflammation. Handb Exp Pharmacol. 2014. ↩︎
Snider AJ, et al. CERK in cancer biology. Adv Cancer Res. 2013. ↩︎
Mikami D, et al. Therapeutic targeting of ceramide kinase. Lipids Health Dis. 2022. ↩︎