UPP2 encodes uridine phosphorylase 2, an enzyme that catalyzes the reversible phosphorylytic cleavage of uridine to uracil and ribose-1-phosphate, which can be utilized as carbon and energy sources or salvaged for pyrimidine nucleotide synthesis. The enzyme accepts a broad range of substrates, including deoxyuridine and other nucleoside analogues. Unlike its homolog UPP1, UPP2 possesses redox-sensitive regulation through a conditional intramolecular disulfide bridge that can inactivate the enzyme by displacing a critical active-site residue, suggesting a role in oxidative stress sensing 1. Recent studies demonstrate that UPP2-mediated ribose salvage from uridine supports glycolysis and ATP production when glucose is limiting, with this pathway active across cancer cells, primary macrophages, and in vivo 2. UPP2 functions as a circadian gene regulated by BMAL1 in liver, and its overexpression inhibits hepatocellular carcinoma cell proliferation and migration in association with p53 upregulation 3. Clinically, UPP2 variants have been identified in pharmacogenetic studies of second-generation antipsychotic-induced metabolic effects in schizophrenia patients 4, and UPP2 expression is associated with response to bladder intracavitary hyperthermic perfusion chemotherapy in non-muscle invasive bladder cancer 5. The gene is also implicated in melanoma progression through alterations in pyrimidine metabolism 6.