{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPhospholipases A2 comprise a diverse family of enzymes with important roles in lipid metabolism and inflammatory signaling. Although enzymes such as lipoprotein‐associated phospholipase A2 (Lp‐PLA2) have been highlighted as markers of unstable atherosclerotic plaques and predictors of stroke (for example, in population‐based studies and cardiovascular disease settings)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ", a distinct member of this family, PLA2G15 (also known as lysosomal phospholipase A2 or LPLA2), displays a unique set of functions.\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn antigen‐presenting cells, PLA2G15 is critical for intracellular lipid homeostasis and immune regulation. It processes complex mycobacterial tetra‐acylated glycolipid antigens into di‐acylated forms that efficiently bind CD1 molecules, an essential step for T‐cell activation against mycobacteria."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPLA2G15 expression in monocytic cells is also subject to transcriptional regulation. Studies in THP‐1 cells demonstrate that retinoids, particularly via a retinoid X receptor (RXR)–dependent pathway, induce PLA2G15 messenger RNA expression and enhance its enzymatic activity, suggesting a link between retinoid signaling, lipid metabolism, and immune cell differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nStructural and biochemical analyses reveal that PLA2G15 exhibits both phospholipase A2 and transacylase activity that is optimal in acidic environments. In crystal studies, Zn²⁺ ions were found to bind within its active site—coordinating key catalytic residues—and induce a closed conformation that inhibits its activity at neutral pH. This pH‐dependent regulation likely ensures robust activity within lysosomes while restricting function in other cellular compartments."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAberrant PLA2G15 functions may contribute to disease. In T‐cell acute lymphoblastic leukemia, an NFATC3‐PLA2G15 chimeric transcript is expressed with reduced NFAT pathway signaling and is associated with aggressive disease biology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Furthermore, studies in the context of cardiopulmonary bypass have shown that elevated urinary PLA2G15 activity correlates with the development of acute kidney injury, highlighting its potential utility as a biomarker for ischemia reperfusion injury."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Brett L Cucchiara, Steve R Messe, Lauren Sansing, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lipoprotein-associated phospholipase A2 and C-reactive protein for risk-stratification of patients with TIA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stroke (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/STROKEAHA.109.553545"}], "href": "https://doi.org/10.1161/STROKEAHA.109.553545"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19461040"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19461040"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "M M Hoffmann, K Winkler, W Renner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variants and haplotypes of lipoprotein associated phospholipase A2 and their influence on cardiovascular disease (The Ludwigshafen Risk and Cardiovascular Health Study)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thromb Haemost (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1538-7836.2008.03216.x"}], "href": "https://doi.org/10.1111/j.1538-7836.2008.03216.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18983494"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18983494"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Martine Gilleron, Marco Lepore, Emilie Layre, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lysosomal Lipases PLRP2 and LPLA2 Process Mycobacterial Multi-acylated Lipids and Generate T Cell Stimulatory Antigens."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Chem Biol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.chembiol.2016.07.021"}], "href": "https://doi.org/10.1016/j.chembiol.2016.07.021"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27662254"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27662254"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Akira Abe, Heather K Poucher, Miki Hiraoka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Induction of lysosomal phospholipase A2 through the retinoid X receptor in THP-1 cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Lipid Res (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1194/jlr.M300342-JLR200"}], "href": "https://doi.org/10.1194/jlr.M300342-JLR200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14754907"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14754907"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Renee A Bouley, Vania Hinkovska-Galcheva, James A Shayman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural Basis of Lysosomal Phospholipase A"}, {"type": "a", "children": [{"type": "t", "text": "sub"}], "href": "sub"}, {"type": "t", "text": "2"}, {"type": "a", "children": [{"type": "t", "text": "/sub"}], "href": "/sub"}, {"type": "t", "text": " Inhibition by Zn"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "2"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": "."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/acs.biochem.8b01124"}], "href": "https://doi.org/10.1021/acs.biochem.8b01124"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30830753"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30830753"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jonathan Bond, Christine Tran Quang, Guillaume Hypolite, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel Intergenically Spliced Chimera, "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "NFATC3-PLA2G15"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": ", Is Associated with Aggressive T-ALL Biology and Outcome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Res (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1541-7786.MCR-17-0442"}], "href": "https://doi.org/10.1158/1541-7786.MCR-17-0442"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29330284"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29330284"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Mario Navarrete, John A Wilkins, Fok Vun Chan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phospholipase A2 group XV activity during cardiopulmonary bypass surgery."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Biochem (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.clinbiochem.2020.12.003"}], "href": "https://doi.org/10.1016/j.clinbiochem.2020.12.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33307060"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33307060"}]}]}]}