Sphingomyelin synthase (SMS) (SMS)

Sphingomyelin synthase (SMS) is a family of enzymes, primarily SMS1 and SMS2, that catalyze the final step of sphingomyelin biosynthesis by transferring a phosphorylcholine group from phosphatidylcholine to ceramide. This reaction is a critical regulatory node in lipid signaling, as it simultaneously controls the levels of pro-apoptotic ceramide and pro-survival diacylglycerol and sphingomyelin (UniProt Q86VZ5, Q8NHU3). SMS1 is localized to the Golgi apparatus and is responsible for the majority of cellular sphingomyelin production, while SMS2 is found at both the Golgi and the plasma membrane, where it regulates local lipid environments and signaling (PMID: 14730305). These enzymes are significant therapeutic targets in metabolic syndrome, atherosclerosis, and cancer. Inhibition of SMS2 has been shown to reduce atherosclerotic plaque formation and improve insulin sensitivity in preclinical models (PMID: 19433515). In oncology, SMS activity is often upregulated to maintain low ceramide levels, thereby evading apoptosis; thus, SMS inhibitors are being explored as potential chemosensitizers to enhance the efficacy of traditional therapies (PMID: 23566330).

Other names

Phosphatidylcholine:ceramide cholinephosphotransferaseSGMSSMS1SMS2Sphingomyelin synthase 1Sphingomyelin synthase 2

Inhibition of the enzymatic transfer of a phosphorylcholine group from phosphatidylcholine to ceramide, reducing sphingomyelin production and increasing ceramide levels.