PLA2G4E is a calcium-dependent N-acyltransferase involved in the biosynthesis of N-acyl ethanolamines (NAEs) in the brain. It transfers the sn-1 fatty acyl chain of phosphatidylcholine, the fatty acyl donor, to the amine group of phosphatidylethanolamine, the acceptor, to generate N-acyl phosphatidylethanolamine (NAPE). It can also use plasmenylethanolamine as an acceptor to form N-acyl plasmenylethanolamine. Both products can act as precursors of bioactive NAEs, including N-arachidonoyl phosphatidylethanolamine, also called anandamide. In addition, the enzyme shows weak phospholipase A2 and lysophospholipase activities.

Beyond lipid metabolism, PLA2G4E regulates intracellular membrane trafficking that depends on changes in membrane curvature, such as enrichment in lysophospholipids. It promotes tubule formation in clathrin-independent endocytic trafficking. These tubules carry internalised clathrin-independent cargo proteins back to the cell surface, so the enzyme contributes to cargo recycling. The protein is found in the cytosol and at early endosome, lysosome and plasma membranes.

The PLA2G4E gene encodes a member of the cytosolic phospholipase A2 group IV family, which HGNC places among the C2 domain containing phospholipases. The previous name was phospholipase A2, group IVE, and the gene was formerly listed under the symbol FLJ45651. A mouse ortholog, Pla2g4e, is recorded. Researchers studying PLA2G4E protein or the PLA2G4E gene typically focus on endocannabinoid precursor synthesis and endocytic recycling.