Ceramide synthase 6 (CERS6)

Ceramide synthase 6 (CERS6) is an integral membrane enzyme of the endoplasmic reticulum responsible for the synthesis of C14- and C16-ceramides by transferring acyl chains from acyl-CoA substrates to sphingoid bases[1][2][3]. It is one of six human ceramide synthases, each with distinct acyl-CoA specificity; CERS6 is notable for its selectivity for palmitoyl-CoA (C16:0) and involvement in producing C16 ceramide, a lipid implicated in cellular apoptosis, metabolic regulation, and pathologies including obesity, insulin resistance, and several forms of cancer[2][3]. The structure of human CERS6 has been resolved by cryo-EM, revealing a seven-transmembrane domain homodimer with a ping-pong catalytic mechanism utilizing a key histidine residue for acyl transfer; its activity is inhibited by mycotoxins such as fumonisin B1, which covalently blocks the active site, providing a foundation for potential therapeutic targeting in metabolic and inflammatory diseases[2][3].

Other names

LASS6CerS6LAG1 longevity assurance homolog 6Sphingoid base N-palmitoyltransferase CERS6LAG1 homologLongevity assurance homolog 6

Inhibition of ceramide synthase enzymatic activity (by covalent modification and prevention of product formation)[2][3]