{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nGroup III secreted phospholipase A₂ (PLA2G3) is an atypical enzyme that, unlike conventional mammalian sPLA₂s, contains unique N‐ and C‐terminal domains flanking a central catalytic domain that is more reminiscent of bee venom PLA₂. Its catalytic activity efficiently hydrolyzes phosphatidylcholine in cell membranes and lipoproteins—generating bioactive lipid mediators such as lysophosphatidylcholine and arachidonic acid metabolites—and thereby modulates lipoprotein composition, promotes foam cell formation, and even exerts antiviral effects by blocking adenoviral entry. In several cellular systems, the central sPLA₂ domain is sufficient to promote arachidonate release and prostaglandin production, while the accessory domains are required for full biological activity and proper localization to target membranes. (​."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPLA2G3 is expressed in a variety of tissues—including neuronal cells, the skin and microvascular endothelium—and its regulation substantially impacts inflammation and cell survival. In neuronal models PLA2G3 facilitates neurite outgrowth and protects against trophic factor deprivation, yet under other conditions its overexpression may trigger apoptotic pathways that exacerbate damage, as seen in models of oxidative stress relevant to neurodegenerative disorders. Moreover, in the skin, transgenic overexpression of PLA2G3 leads to spontaneous dermatitis with robust infiltration of inflammatory cells and upregulation of pro-inflammatory cytokines. 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