PLAAT2 (phospholipase A and acyltransferase 2) is a calcium-independent phospholipid-metabolizing enzyme with dual enzymatic functions. It catalyzes phospholipase A1/2 activity, releasing fatty acids from the sn-1 or sn-2 positions of glycerophospholipids, with substantially higher PLA1 activity than PLA2 for most substrates 1. PLAAT2 also exhibits N-acyltransferase activity, transferring fatty acyl groups from phosphatidylcholine to phosphatidylethanolamine to form N-acylphosphatidylethanolamine (NAPE), a precursor for bioactive N-acylethanolamines (NAEs) involved in food intake, pain, and inflammation regulation 23. PLAAT2 demonstrates remarkable functional complexity: heterologous expression in engineered bacteria conferred persistent obesity resistance, validating NAPEs as its primary bioactive product 3. Disease relevance varies by tissue context. In pancreatic cancer, PLAAT2 is substantially elevated and promotes tumor progression through lipid-metabolic pathway enrichment, correlating with advanced grade/stage, poor survival, and chemotherapy resistance 4. Conversely, PLAAT2 functions as a tumor suppressor in gastric cancer, where downregulation associates with poor prognosis; mechanistically, PLAAT2 facilitates cMyc ubiquitination via TRIM32 recruitment to inhibit oncogenic MEK/ERK signaling 5. These contrasting roles highlight tissue-specific functions. Clinically, PLAAT2 and PLAAT2-derived transcriptional signatures serve as potential prognostic biomarkers and therapeutic targets, with selective PLAAT2 inhibitors like LEI-301 offering pharmacological tools for pathway dissection 2.