PLA2G7 encodes lipoprotein-associated phospholipase A2 (Lp-PLA2), a calcium-independent phospholipase that catalyzes phospholipid hydrolysis at the sn-2 position, with particular specificity for oxidized and short-chain lipids. The enzyme degrades platelet-activating factor (PAF), a potent pro-inflammatory mediator, and processes oxidized phospholipids in low-density and high-density lipoprotein particles, thereby modulating inflammatory and oxidative stress responses. PLA2G7 has been extensively investigated in cardiovascular disease. Although elevated Lp-PLA2 activity correlates with multiple coronary heart disease risk markers, with hazard ratios of 1.61 for the top versus bottom activity quartile, genetic variants in PLA2G7 show inconsistent associations with disease risk 1. Mendelian randomization analysis identified PLA2G7 as a key mediator linking fasting insulin to coronary artery disease, explaining approximately 19.5% of insulin's total effect 2. Serum Lp-PLA2 levels demonstrated excellent diagnostic ability (AUC 0.935) for predicting coronary artery disease risk and severity 3. Recent evidence extends PLA2G7's pathogenic roles beyond cardiovascular contexts. PLA2G7 inhibition by darapladib reduces profibrotic macrophage differentiation in silicosis through restoration of cardiolipin-mediated mitophagy 4, restrains osteoclast differentiation and prevents bone loss via the Alox12/12-HETE/Gpr31 axis 5, and reverses immunosuppression in hepatocellular carcinoma, enhancing anti-PD-1 immunotherapy efficacy 6. PLA2G7 also influences idiopathic pulmonary fibrosis progression through macrophage-driven immune dysregulation 7 and associates with dementia risk as a mediator of Alzheimer's disease polygenic risk 8. Darapladib and rilapladib represent the primary therapeutic approaches targeting this enzyme.