PNPLA-mediated lipid hydrolysis and transacylation – At the intersection of catabolism and anabolism.

Patatin-like phospholipase domain containing proteins (PNPLAs) play diverse roles in lipid metabolism. In this review, we focus on the enzymatic properties and predicted 3D structures of PNPLA1-5. PNPLA2-4 exert both catabolic and anabolic functions. Whereas PNPLA1 is predominantly expressed in the epidermis and involved in sphingolipid biosynthesis, PNPLA2 and 4 are ubiquitously expressed and exhibit several enzymatic activities, including hydrolysis and transacylation of various (glycero-)lipid species. This review summarizes known biological roles for PNPLA-mediated hydrolysis and transacylation reactions and highlights open questions concerning their physiological function. • PNPLA2-4 exert both catabolic and anabolic functions as hydrolases and transacylases. • PNPLA1 is only described as a transacylase and is crucial for acylceramide biosynthesis. • PNPLA5 is only described as a possible TAG hydrolase. • Open questions include the physiological relevance of trancylation processes of PNPLA2-4. • The regulation of the balance between hydrolysis and transacylation also needs to be investigated in more detail. • The role of transacylation in the biosynthesis of other bioactive lipids besides FAHFAs still requires further studies. [ABSTRACT FROM AUTHOR]