PLA2G4C encodes cytosolic phospholipase A2 gamma (cPLA2-gamma), a calcium-dependent phospholipid-hydrolyzing enzyme located on chromosome 19.3 1. The protein functions primarily in phospholipid remodeling and lipid metabolism, with enzymatic activity required for its biological effects 2. Mechanistically, PLA2G4C catalyzes the release of fatty acids from phospholipids, including arachidonic acid for prostaglandin and leukotriene biosynthesis 3. During hepatitis C virus (HCV) infection, PLA2G4C expression is upregulated via NF-κB and c-Myc activation 4. This upregulation alters lipid droplet (LD) phospholipid composition by reducing phosphatidylcholine levels, stabilizing and enlarging LDs and promoting HCV replication 24. Both membrane attachment (residues 260-292) and enzymatic activity are required for LD biogenesis 2. Disease relevance includes: HCV-associated hepatic steatosis through altered LD dynamics 4; preterm birth risk through prostaglandin regulation 5; colorectal cancer prognosis, where the A allele of rs1549637 associates with worse survival, especially in stage II disease (HR 3.84) 3; schizophrenia genetic susceptibility 6; and lung cancer through non-coding regulatory mechanisms 7. Clinically, PLA2G4C polymorphisms may serve as prognostic biomarkers for colorectal cancer treatment planning and as diagnostic markers for 19q chr19 loss in gliomas 13.