ALOX12 encodes arachidonate 12-lipoxygenase, an enzyme that catalyzes the oxidation of polyunsaturated fatty acids to generate bioactive lipid metabolites, particularly converting arachidonic acid to 12-hydroxyeicosatetraenoic acid (12-HETE) 1. The enzyme plays crucial roles in ferroptosis, a form of programmed cell death characterized by lipid peroxidation. ALOX12 is essential for p53-mediated tumor suppression through a distinct ferroptosis pathway independent of GPX4 2. Loss of ALOX12 function accelerates tumorigenesis, and missense mutations found in human cancers abolish its ability to induce ferroptosis 2. In pathological contexts, ALOX12 mediates tissue damage through the ALOX12-12-HETE-GPR31 signaling axis, contributing to hepatic ischemia-reperfusion injury 1, lung ischemia-reperfusion injury via endothelial ferroptosis and neutrophil extracellular trap formation 3, and cisplatin-induced acute kidney injury 4. The enzyme also regulates bone homeostasis by promoting osteoclast differentiation through the same signaling pathway 5. Additionally, ALOX12 is associated with premature ovarian insufficiency, suggesting roles in reproductive function 6. Its dual role as both a tumor suppressor through ferroptosis induction and a mediator of tissue injury makes ALOX12 a significant therapeutic target.