UPRT (uracil phosphoribosyltransferase) is a pyrimidine salvage pathway enzyme that catalyzes the conversion of uracil to uridine monophosphate (UMP) 1. The enzyme is highly conserved from prokaryotes to humans, though phylogenetic evidence suggests that UPRT homologs from higher eukaryotes, including humans, may have altered substrate specificity compared to microbial versions 1. In Drosophila, UPRT is essential for larval growth, pre-pupal/pupal viability, and normal adult lifespan, indicating the enzyme maintains important physiological functions in higher eukaryotes despite evolutionary changes 1. Therapeutically, microbial UPRT has been exploited in suicide gene therapy approaches for cancer treatment. The enzyme converts the prodrug 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU), which is then further metabolized to cytotoxic fluorinated nucleotides 23. This CD::UPRT fusion system demonstrates significant bystander effects, killing both transduced and surrounding tumor cells 24. Clinical applications include adenoviral-mediated gene therapy for colorectal cancer and glioblastoma, where UPRT expression enhances 5-FU chemosensitivity by 13-70 fold 34. Recent approaches utilize extracellular vesicles containing UPRT for cell-free gene therapy delivery 56.