PAOX is a flavoenzyme that catalyzes the oxidation of N(1)-acetylspermine to spermidine and N(1)-acetylspermidine to putrescine, playing a central role in polyamine catabolism and back-conversion. Recent evidence suggests that PAOX expression is extremely low in most tumor and non-tumor cell lines, with enzymatic activity detectable mainly in neuroblastoma and low-passage glioblastoma cells, and that polyamine level reduction occurs predominantly through acetylpolyamine secretion rather than back-conversion 1. PAOX dysregulation is implicated in multiple malignancies: copy number gains with coordinated upregulation occur in primary myelofibrosis 2, and PAOX expression is suppressed in bladder cancer compared to normal tissues 3. In estrogen receptor-positive breast cancer cells, 17β-estradiol downregulates PAOX expression via estrogen receptor 2 4. PAOX polymorphisms (rs1046175) affect diagnostic value of polyamine biomarkers in non-small-cell lung cancer 5. Beyond cancer, PAOX upregulation in intervertebral disc degeneration contributes to oxidative stress and cell senescence; spermidine supplementation rebalances polyamine metabolism and delays degeneration in mice 6. In non-obstructive azoospermia, PAOX was identified as a potential biomarker among five core regulatory genes 7. PAOX overexpression correlates with cancer cell resistance to genotoxic drugs 1, positioning it as a therapeutic target in multiple disease contexts.