ALOX5 (arachidonate 5-lipoxygenase) catalyzes the oxygenation of arachidonate to 5-hydroperoxyeicosatetraenoate (5-HPETE) and subsequently to leukotriene A4 (LTA4), initiating leukotriene biosynthesis and inflammatory responses. Beyond inflammation, ALOX5 metabolizes oxidized fatty acids to generate specialized pro-resolving mediators including lipoxins and resolvins, supporting anti-inflammatory and pro-resolving functions. The enzyme participates in immune regulation by modulating dendritic cell migration, monocyte adhesion, and humoral immunity through B cell and follicular helper T cell regulation. In disease contexts, ALOX5 dysregulation contributes to multiple pathologies. Low ALOX5 expression promotes ferroptosis escape in bladder cancer, enabling cancer cell survival 1, while elevated ALOX5 drives pancreatic cancer progression by fostering M2 macrophage polarization via JAK/STAT pathway activation 2. In glioma, ALOX5-derived 5-HETE promotes immunosuppressive M2 polarization of glioma-associated microglia/macrophages and PD-L1 expression 3. ALOX5 overexpression also contributes to atherosclerosis by regulating macrophage ferroptosis 4, and in cardiac pathology, high ALOX5 levels promote ventricular hypertrophy independent of enzymatic activity by modulating Runx2 phase separation 5. In COPD, elevated ALOX5 and its metabolite LTA4 accumulate through monocyte infiltration, triggering ferroptosis-promoting gene expression in lung epithelium 6. These findings establish ALOX5 as a critical metabolic hub linking lipid mediator production to immune cell polarization and disease progression.