UPP2 (uridine phosphorylase 2) catalyzes the reversible phosphorylytic cleavage of uridine to uracil and ribose-1-phosphate, with broad substrate specificity including deoxyuridine and related compounds 12. This enzyme plays a critical role in nucleotide salvage and energy metabolism; when glucose is limiting, UPP1/UPP2-mediated cleavage of uridine enables ribose salvage through the pentose phosphate pathway to support glycolysis and ATP production 3. UPP2 possesses unique redox sensitivity through an intramolecular disulfide bridge mechanism absent in UPP1, allowing conditional inactivation via oxidative stress sensing 2. Clinically, UPP2 variants are associated with antipsychotic-induced metabolic side effects in schizophrenia patients 4 and have been identified as a circadian-regulated gene linked to hepatocellular carcinoma development, where UPP2 overexpression inhibits HepG2 cell proliferation and migration 5. Additionally, UPP2 is enriched in somatic mutations in melanoma progression, contributing to dysregulated pyrimidine metabolism 6. These findings establish UPP2 as a multifunctional enzyme integrating nucleotide metabolism, redox regulation, and disease pathogenesis, with emerging therapeutic potential in cancer prevention and metabolic disorder management.