SMOX (spermine oxidase) is a flavoenzyme that catalyzes polyamine catabolism, converting spermine to spermidine and regulating intracellular polyamine concentration 1. This catalytic activity has broad implications for cellular homeostasis and disease pathogenesis across multiple organ systems. In cancer biology, SMOX has emerged as a key driver of tumorigenesis through multiple mechanisms. SMOX stabilization via YBX1-mediated mRNA stabilization promotes esophageal squamous cell carcinoma progression through mTORC1 pathway activation 2. Similarly, in gastric cancer, SMOX-catalyzed spermine degradation generates acrolein, a reactive electrophile that induces DNA damage and promotes Helicobacter pylori-mediated carcinogenesis 3. In renal cell carcinoma, the PUS1-SMOX axis regulates cell migration through mRNA pseudouridylation-mediated stabilization 4. Conversely, SMOX inhibition offers therapeutic potential in inflammatory and fibrotic diseases. Reduced SMOX expression correlates with colitis severity, and SMOX-mediated spermidine generation protects against colitis-associated carcinoma and dysbiosis 1. In chr20 kidney disease, elevated renal SMOX contributes to fibrosis and senescence; SMOX inhibition or spermine supplementation restores autophagy and reduces pathology 5. Additionally, SMOX inhibition alleviates acute kidney injury by reducing oxidative stress and tubular injury 6, and suppresses age-related cellular senescence by limiting acrolein-mediated DNA damage 7.