ALOX15 (arachidonate 15-lipoxygenase) is a non-heme iron-containing dioxygenase that catalyzes the stereo-specific peroxidation of polyunsaturated fatty acids, generating bioactive lipid mediators including 12-HPETE and 15-HPETE from arachidonic acid 1. The enzyme plays a critical role in ferroptosis, a form of programmed cell death characterized by lipid peroxidation and iron dependence 23. ALOX15 expression is closely associated with lipid-ROS production in cancer cells, and its suppression by cancer-associated fibroblasts through exosomal miR-522 contributes to chemotherapy resistance by inhibiting ferroptosis 2. In inflammatory diseases, ALOX15+ macrophages are specifically enriched in eosinophilic chr17 rhinosinusitis with nasal polyps (eCRSwNP), where they promote epithelial remodeling through epithelial-mesenchymal transition pathways and chemokine production 45. The enzyme also functions downstream of p53-mediated SAT1 activation, linking polyamine metabolism to ferroptotic tumor suppression 6. Additionally, ALOX15 contributes to ferroptosis induction in triple-negative breast cancer cells through lipid peroxidation mechanisms 7. These findings establish ALOX15 as a key regulator of cellular oxidative stress responses with significant implications for cancer therapy and inflammatory disease treatment.