LIPE (lipase E, hormone sensitive type) is a hormone-sensitive lipase with broad substrate specificity that catalyzes the hydrolysis of multiple lipid classes including triacylglycerols (TAGs), diacylglycerols (DAGs), monoacylglycerols (MAGs), cholesteryl esters, and retinyl esters. The enzyme shows preferential hydrolysis of DAGs over TAGs and MAGs, with specificity for fatty acid esters at the sn-3 position of the glycerol backbone in DAGs. In adipose tissue and heart, LIPE primarily hydrolyzes stored triglycerides to release free fatty acids, while in steroidogenic tissues it converts cholesteryl esters to free cholesterol for steroid hormone synthesis [33794741]. The enzyme also catalyzes hydrolysis of endocannabinoids and lipid precursors involved in inflammatory signaling pathways. LIPE localizes to the cytosol and lipid droplets, where it functions in lipid catabolism and energy mobilization. Mutations in LIPE are associated with familial partial lipodystrophy type 6, highlighting the critical role of this enzyme in normal lipid metabolism and adipose tissue function. The hormone-sensitive regulation of LIPE activity enables dynamic control of lipid breakdown in response to metabolic demands.