LPCAT2 (lysophosphatidylcholine acyltransferase 2) is a bifunctional enzyme catalyzing acyltransferase and acetyltransferase reactions on the endoplasmic reticulum and lipid droplets 123. It converts lysophosphatidylcholine to phosphatidylcholine and lysophosphatidic acid to phosphatidic acid, while also catalyzing platelet-activating factor (PAF) biosynthesis from lyso-PAF precursors 13. Under inflammatory stimulation, LPCAT2 acetyltransferase activity increases, promoting PAF synthesis 4. LPCAT2 regulates lipid droplet accumulation, which has emerged as therapeutically significant in cancer biology 567. Disease relevance spans multiple pathologies. In colorectal cancer, LPCAT2 suppresses tumor progression by inducing ferroptosis through the PRMT1/SLC7A11 axis; conversely, high LPCAT2 expression drives chemoresistance via lipid droplet accumulation that impairs caspase activation 86. In pancreatic cancer, LPCAT2-mediated lipid droplet production promotes gemcitabine resistance and cell motility via STAT5B activation 7. LPCAT2 upregulation correlates with unfavorable prognosis across multiple cancer types 9. In sepsis-induced acute lung injury, lactate-driven LPCAT2 lactylation exacerbates ferroptosis through STAT1/SLC7A11 suppression 10. LPCAT2 expression associates with both pain susceptibility and Alzheimer's disease progression in sex- and APOE-dependent manners 11. Clinically, LPCAT2 represents a druggable target for restoring chemotherapy sensitivity and modulating inflammatory responses in multiple disease contexts.