Figure 2. Specificity of ceramide synthase(s) and the diversity of ceramide species.

The de novo synthesis of various chain length fatty acids containing ceramide are formed by the action of specific CerS. CerS1 specifically biosynthesizes C₁₈ -ceramide; CerS2 and CerS4 mediate very-long-chain fatty acid-containing ceramide synthesis, such as C₂₂-, C₂₄- and C₂₆-ceramides. Additionally, CerS5 and CerS6 are mostly responsible for the synthesis of chain lengths up to 16, such as C₁₂-, C₁₄- and C₁₆-ceramides. Ceramide is the precursor for S1P. Importantly, these two molecules have opposing functions and are known to regulate each other. In addition, ceramides with different chain lengths might have distinct and sometimes opposing functions in the regulation of tumor progression and/or growth. For example, in HNSCC tumors, while CerS1-generated C₁₈-ceramide inhibits tumor growth, CerS6-mediated C₁₆-ceramide induces tumor growth.

CerS: Ceramide synthase; DES: Desaturase; HNSCC: Head and neck squamous cell carcinoma; S1P: Sphingosine-1-phosphate.