{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPhospholipase A1A (PLA1A) and its related isoforms, including the intracellular iPLA1γ, constitute a family of lipid‐modifying enzymes that mediate critical aspects of membrane dynamics. For example, iPLA1γ is involved in a specific Golgi‐to–endoplasmic reticulum retrograde membrane transport pathway, underscoring its role in maintaining intracellular membrane organization."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, during hepatitis C virus infection PLA1A is upregulated and facilitates viral assembly by stabilizing and bridging interactions among structural and nonstructural viral proteins (E2, NS2, and NS5A), as well as promoting TBK1 activation via its interaction with MAVS."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "4"}]}, {"type": "t", "text": " Furthermore, investigation of genetic polymorphisms in the PLA1A gene has provided insights into its variations and potential links with metabolic traits."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPLA1A also catalyzes the hydrolysis of phosphatidylserine to generate lysophosphatidylserine (lysoPS), a bioactive lipid mediator that influences diverse cellular responses. Elevation in lysoPS levels via PLA1A is implicated in oncogenesis and metastasis in several cancer types. For instance, enhanced PLA1A activity has been associated with colorectal cancer progression"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", gastric cancer where a PS-PLA1–mediated pathway may contribute to lysoPS production"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", hepatocellular carcinoma with serum enzyme levels correlating with liver injury"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", and melanoma where increased PLA1A levels correlate with disease severity and BRAF mutations."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Additionally, PLA1A expression is upregulated in macrophages following TLR4 stimulation and may serve as an indicator of inflammatory processes such as those observed in chronic allograft rejection."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its catalytic functions, PLA1A shows promise as a biomarker in systemic diseases and as a modulator of immune responses. In autoimmune rheumatic conditions, for example, elevated levels of PLA1A in plasma and synovial fluid are associated with enhanced inflammatory signaling via conversion of lysoPS to lysophosphatidic acid (LPA) and subsequent activation of LPA receptor-mediated pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Moreover, studies in thyroid disorders have highlighted associations between aberrant PLA1A levels and disease, broadening its clinical relevance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " In lung adenocarcinoma, overexpression of PLA1A suppresses cell proliferation and migratory/invasive behavior—mediated via elevated lysoPS that activates the G-protein-coupled receptor 174 and downstream cAMP/protein kinase A signaling, thereby inducing S-phase arrest and inhibiting epithelial-mesenchymal transition."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Rei K Morikawa, Junken Aoki, Fumi Kano, et al. 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