Upp2, also known as uridine phosphorylase 2, is an enzyme that catalyzes the reversible conversion of uridine to uracil and ribose-1-phosphate. It is involved in the pyrimidine salvage pathway, which plays a critical role in nucleotide metabolism. This pathway is essential for cells to recycle nucleotides and maintain the balance of nucleotide pools, which is crucial for DNA and RNA synthesis, energy metabolism, and cell survival [4].

In a study on nutrient-limited conditions, it was found that the catabolism of uridine, where UPP1/UPP2 phosphorylytically cleaves uridine into uracil and ribose-1-phosphate, can support glycolysis. The ribose moiety from uridine or RNA can be salvaged to meet energy requirements via the pentose phosphate pathway and glycolysis [1]. Another study showed that in mice, overexpression of hepatic MIC19 led to increased UPP2 activity, causing uracil accumulation in the liver, which was associated with increased energy expenditure and pedestrian locomotion [2]. In the context of circadian rhythms and hepatocellular carcinoma, Upp2 was identified as a BMAL1-regulated gene. Overexpression of human UPP2 protein inhibited the proliferation and migration of HepG2 cells, suggesting its potential role in HCC prevention and treatment [3].

In conclusion, Upp2 is crucial in nucleotide metabolism and has far-reaching impacts on energy metabolism, locomotion, and potentially in cancer-related processes. Studies using mouse models have revealed its role in these biological functions and disease-related conditions, providing valuable insights into the underlying mechanisms and potential therapeutic targets.