PLA2G15 is a lysosomal phospholipase A2 enzyme with dual phospholipase and O-acyltransferase activities that plays crucial roles in lysosomal lipid homeostasis 1. The enzyme exhibits calcium-independent activity with an acidic pH optimum and preferentially hydrolyzes the sn-1 fatty acyl group of phospholipids, including phosphatidylcholines, phosphatidylethanolamines, and phosphatidylglycerols 1. Mechanistically, PLA2G15 serves as a key regulator of bis(monoacylglycero)phosphate (BMP) catabolism in lysosomes, where it acts as a physiological BMP hydrolase essential for lysosomal lipid turnover 23. The enzyme can transfer fatty acyl groups to lipophilic alcohols and is involved in processing oxidized phospholipids during oxidative stress 1. Disease relevance is significant, as PLA2G15 dysfunction contributes to multiple pathological conditions. The enzyme is inhibited by glycerophosphodiesters in Batten disease, leading to toxic lysophospholipid accumulation 4. Additionally, PLA2G15 inhibition by cationic amphiphilic drugs predicts drug-induced phospholipidosis 5. Clinically, targeting PLA2G15 shows therapeutic potential - its inhibition ameliorates Niemann-Pick disease type C1 pathologies and extends lifespan in mouse models 2. The enzyme also promotes healthy aging, as its suppression improves healthspan in C. elegans 6.