OAZ1 encodes ornithine decarboxylase antizyme 1, a negative regulator of polyamine metabolism that controls intracellular polyamine levels through multiple mechanisms. OAZ1 binds ornithine decarboxylase (ODC) monomers to prevent assembly of the active ODC homodimer and targets monomers for proteasomal degradation by exposing a cryptic proteasome-interacting surface. It also inhibits polyamine uptake by inactivating cellular polyamine transporters. Beyond polyamine regulation, OAZ1 participates in a SMAD1/PSMB4 complex that mediates degradation of the transcriptional repressor SNIP1, and facilitates AZIN2 translocation from the ER-Golgi compartment to the cytosol. Dysregulation of polyamine homeostasis is implicated in multiple cancers and neurodegeneration. In non-small cell lung cancer, OAZ1 expression is suppressed in cisplatin-resistant cells; HDAC inhibitor S11 restores OAZ1 expression and resensitizes resistant cells to cisplatin treatment. An OAZ1-CSNK1G2 fusion has been detected in mucinous breast cancer. OAZ1 genetic variants, particularly the +2222A/G polymorphism, associate with coronary in-stent restenosis and coronary heart disease risk in vascular disease contexts. Salivary OAZ1 expression shows diagnostic potential for oral squamous cell carcinoma when combined with other biomarkers, achieving 100% predictive accuracy in a cohort study. Recent evidence links polyamine dysregulation to both Parkinson's disease and cancer progression, positioning polyamine metabolism as a therapeutic target.