UPP1 (uridine phosphorylase 1) catalyzes the reversible phosphorylytic cleavage of uridine to uracil and ribose-1-phosphate, enabling cells to utilize uridine-derived ribose as an alternative carbon and energy source 1. This enzyme plays a critical role in nutrient-limited conditions, where uridine-derived ribose can bypass upper glycolysis to fuel ATP production, biosynthesis, and gluconeogenesis through the pentose phosphate pathway and glycolytic utilization 1. In pancreatic ductal adenocarcinoma, UPP1 expression is regulated by KRAS-MAPK signaling and supports tumor survival and proliferation under glucose restriction 2. The enzyme demonstrates significant disease relevance across multiple cancer types. In lung adenocarcinoma, UPP1 promotes tumor progression by creating an immunosuppressive microenvironment through increased TGF-β1 release and PD-L1 expression via the PI3K/AKT/mTOR pathway 3. In bladder cancer, UPP1 enhances cell proliferation, invasion, and gemcitabine resistance by activating AKT signaling 4. High UPP1 expression correlates with poor survival in pancreatic cancer patients and mediates immune checkpoint blockade resistance by depleting uridine in the tumor microenvironment 25. Additionally, UPP1 shows protective effects in sepsis-induced acute lung injury by inhibiting macrophage ferroptosis through Nrf2 signaling activation 6.