ODC1 (ornithine decarboxylase 1) catalyzes the rate-limiting step of polyamine biosynthesis, converting ornithine to putrescine, the precursor for spermidine and spermine 1. As a pyridoxal phosphate-dependent enzyme, ODC1 is essential for cell proliferation and regulates multiple cellular processes including DNA replication and apoptosis. Mechanistically, ODC1 functions at critical metabolic intersections. It bridges nitric oxide and polyamine metabolism in inflammatory macrophages downstream of NOS2 2, and serves as a transcriptional target for multiple signaling pathways including Nrf2 3, AhR 4, HIF-1 5, and HIVEP1 6. ODC1-dependent polyamine synthesis regulates diverse physiological processes: suppressing osteoclast differentiation via the iron-ornithine axis 3, amplifying ferroptosis in cancer cells through H2O2-dependent mechanisms 1, promoting TH17 cell differentiation in NASH pathogenesis 6, and mediating fasting-induced autophagy through spermidine-dependent EIF5A hypusination 7. Clinically, ODC1 dysregulation associates with multiple diseases. ODC1 inhibition protects against Alzheimer's disease-related memory impairment 8, while its upregulation promotes chemotherapy-induced breast cancer stem cell enrichment 5. These findings position ODC1 as a therapeutic target across cancer, neurodegenerative, inflammatory, and metabolic diseases.