PLA2G4B is a calcium-dependent phospholipase A1/A2 that catalyzes ester bond hydrolysis of phospholipids at the sn-1 or sn-2 positions, generating lysophospholipids and free fatty acids 1. This enzyme participates in arachidonic acid metabolism and lipid remodeling across multiple cellular compartments including the cytosol, mitochondrial inner membrane, and extracellular regions. Mechanistically, PLA2G4B functions in lipid metabolism pathways that regulate cellular signaling. In colorectal cancer, PLA2G4B is transcriptionally regulated by FASN via the SP1/PLA2G4B axis, promoting phosphatidylcholine (PC) metabolism and driving cancer cell proliferation, migration, and invasion while suppressing natural killer cell antitumor responses 2. Similarly, PLA2G4B regulates the alpha-linolenic acid metabolic pathway in type 2 diabetes pathogenesis 3. PLA2G4B demonstrates significant disease relevance across multiple conditions. In psoriasis, PLA2G4B inhibition suppresses keratinocyte proliferation and reduces inflammatory responses through modulation of sphingolipid and ceramide pathways, with therapeutic effects comparable to betamethasone 4. In head and neck squamous cell carcinoma, the JMJD7-PLA2G4B fusion gene promotes cell survival through AKT phosphorylation and cell cycle progression via SKP2-mediated p21/p27 suppression 5. Clinically, elevated PLA2G4B expression in prostate cancer independently correlates with longer disease-free survival and favorable prognostic indicators 1. Additionally, PLA2G4B downregulation with aging is associated with longevity phenotypes, suggesting its role in lifespan regulation 6.