Ceramide synthases as potential targets for therapeutic intervention in human diseases

• Ceramide is generated by a family of six ceramide synthases (CerS).
• Each CerS generates ceramides with defined acyl chain lengths.
• CerS null mice show tissue-specific pathology.
• Ceramide species with defined acyl chain lengths are involved in a number of diseases.
• CerS might potentially be targets for therapeutic intervention.

Ceramide is located at a key hub in the sphingolipid metabolic pathway and also acts as an important cellular signaling molecule. Ceramide contains one acyl chain which is attached to a sphingoid long chain base via an amide bond, with the acyl chain varying in length and degree of saturation. The identification of a family of six mammalian ceramide synthases (CerS) that synthesize ceramide with distinct acyl chains, has led to significant advances in our understanding of ceramide biology, including further delineation of the role of ceramide in various pathophysiologies in both mice and humans. Since ceramides, and the complex sphingolipids generated from ceramide, are implicated in disease, the CerS might potentially be novel targets for therapeutic intervention in the diseases in which the ceramide acyl chain length is altered. This article is part of a Special Issue entitled New Frontiers in Sphingolipid Biology.