Ceramide synthase 4 (CerS4)

Ceramide synthase 4 (CerS4) is a membrane-bound enzyme encoded by the CERS4 gene that catalyzes the N-acylation of sphingosine (or sphinganine) with fatty acyl-CoA, specifically generating ceramides with C18–C22 acyl chains. CerS4 is mainly expressed in skin, muscle, heart, liver, and leukocytes, though at lower levels than other ceramide synthases. It plays a central role in sphingolipid metabolism, cell proliferation, and apoptosis. Overexpression is associated with tumor growth and poor outcomes in several human malignancies, notably breast and liver cancer, and it may contribute to processes in neurodegenerative diseases. CerS4 has also been implicated in the regulation of apoptosis and signaling pathways such as NF-κB, Akt/mTOR, and β-catenin, depending on the cellular context. Due to its roles in disease, CerS4 is being explored as a therapeutic target and biomarker, although direct drugs specifically targeting CerS4 are not yet in clinical use.

Other names

CERS4TRH1CerS-4Ceramide synthase isoform 4

Inhibition of CerS4 may reduce ceramide synthesis, altering apoptosis and cell proliferation, particularly in cancer cells. Inhibitors (e.g., fumonisin B1) block ceramide synthase activity, interrupting sphingolipid biosynthesis and associated signaling pathways.