UMPS (uridine monophosphate synthase) is a bifunctional enzyme catalyzing the final two steps of de novo pyrimidine biosynthesis. It possesses dual enzymatic activities: orotate phosphoribosyltransferase (OPRT), which converts orotate to orotidine-5'-monophosphate (OMP), and orotidine-5'-monophosphate decarboxylase (ODC), which decarboxylates OMP to produce uridine monophosphate (UMP) 1. UMPS activity is subject to metabolic regulation; uric acid, which is 10-fold higher in human plasma than in rodent blood, directly inhibits UMPS and consequently reduces pyrimidine synthesis 2. UMPS expression can be enhanced through Akt/β-catenin signaling pathways and is upregulated in hepatocellular carcinoma to support increased pyrimidine metabolism and cancer progression 3. Clinically, biallelic UMPS mutations cause hereditary orotic aciduria type 1, presenting with megaloblastic anemia, neutropenia, and developmental delays in infancy, treatable with uridine supplementation 1. Heterozygous UMPS variants result in mild orotic aciduria without clinical consequences 1. UMPS expression levels influence chemotherapy sensitivity; enhanced UMPS expression via the SNORD3A-miR-185-5p axis specifically sensitizes breast cancer cells to 5-fluorouracil 4. Phosphorylation of UMPS fine-tunes its activity in response to metabolic demands 5.