{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n 5‐lipoxygenase (5‐LO), encoded by the ALOX5 gene, is a pivotal enzyme that oxygenates arachidonic acid to produce leukotrienes – potent lipid mediators that regulate inflammation and immune responses. Several studies have demonstrated that ALOX5‐driven leukotriene biosynthesis contributes to the pathogenesis of cardiovascular diseases by promoting macrophage‐driven inflammatory cascades, enhancing matrix metalloproteinase expression, and destabilizing atherosclerotic plaques."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In addition, elevated ALOX5 expression has been linked to tumorigenesis in diverse tissues; its up‐regulation in colonic neoplasms and pancreatic cancer tissues supports a role in sustaining chronic inflammation and cell proliferation, while inhibition of ALOX5 activity reduces cancer cell growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, genetic ablation of ALOX5 impairs the function and survival of leukemia stem cells in chronic myeloid leukemia, thereby preventing disease initiation and progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " ALOX5 also exerts immunomodulatory effects during infection by generating lipoxins that temper proinflammatory cytokine production, as observed in models of Toxoplasma gondii–induced inflammation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Structural and mechanistic studies have further elucidated the importance of its membrane‐targeting domains in determining subcellular localization and optimizing its enzymatic activity"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", and recent work contrasting natural product inhibitors has revealed allosteric sites that provide novel opportunities for selective modulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " In addition, interactions with redox regulators, such as MGST1, have been shown to attenuate ALOX5‐mediated lipid peroxidation and confer resistance to ferroptosis in pancreatic ductal adenocarcinoma cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Finally, genetic polymorphisms in ALOX5 influence individual responses to leukotriene‐modifying therapies in asthma, underscoring its clinical relevance as a therapeutic target in various inflammatory and neoplastic disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Margarete Mehrabian, Hooman Allayee, Jack Wong, et al. 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