Regulation of lipid droplet dynamics and lipid homeostasis by hydroxysteroid dehydrogenase proteins

The superfamily of hydroxysteroid dehydrogenases (HSDs) has been wellcharacterized as enzymes in lipid metabolism, and especially in steroid hormone metabolism from bacteria to mammals. Recently, a subset of HSDs members, including 3(3-HSD, 11(3-HSD, and 17(3-HSD, have been shown to be lipid droplet (LD)-associated proteins that are involved in LD dynamics beyond their canonical functions. This review summarizes current understanding of these LDassociated HSD proteins, focusing on how they regulate different LDs with respect to distinct neutral lipids including triacylglycerols (TAGs), cholesterol esters (CEs), and retinyl esters (REs), the evolutionally conserved role of some LD-associated 17(3-HSDs in preventing lipolysis, and specific targeting of HSDs for the treatment of metabolic diseases and viral infections.