UPB1 encodes β-ureidopropionase, a zinc-binding enzyme catalyzing the final step of pyrimidine degradation 1. It converts N-carbamoyl-β-alanine into β-alanine, ammonia, and CO2, and similarly processes N-carbamoyl-β-aminoisobutyrate 2. The enzyme functions as a homotetramer in the cytosol 3. UPB1 deficiency presents with variable clinical phenotypes. While associated with neurodevelopmental features including intellectual disability, seizures, and autism 4, the relationship between UPB1 variants and clinical disease remains uncertain. Notably, the most frequently reported pathogenic variant, p.Arg326Gln, is highly prevalent in East Asian populations (carrier frequency 1:19), questioning its pathogenic significance 4. Currently, UPB1 is considered a gene of uncertain clinical significance 4. Clinically, low UPB1 expression correlates with poor prognosis in lung adenocarcinoma, associated with lymph node metastasis and reduced overall survival 5. In cancer chemotherapy, UPB1 variants may modestly contribute to fluoropyrimidine toxicity, with the c.-80C>G variant associated with severe mucositis (OR=7.5) 6. However, UPB1 alterations appear less significant than DPYD variants in determining chemotherapy toxicity 6.