Emerging roles and therapeutic potentials of sphingolipids in pathophysiology: emphasis on fatty acyl heterogeneity.

Sphingolipids not only exert structural roles in cellular membranes, but also act as signaling molecules in various physiological and pathological processes. A myriad of studies have shown that abnormal levels of sphingolipids and their metabolic enzymes are associated with a variety of human diseases. Moreover, blood sphingolipids can also be used as biomarkers for disease diagnosis. This review summarizes the biosynthesis, metabolism, and pathological roles of sphingolipids, with emphasis on the biosynthesis of ceramide, the precursor for the biosynthesis of complex sphingolipids with different fatty acyl chains. The possibility of using sphingolipids for disease prediction, diagnosis, and treatment is also discussed. Targeting endogenous ceramides and complex sphingolipids along with their specific fatty acyl chain to promote future drug development will also be discussed.