UROC1 encodes urocanate hydratase (urocanase), a cytosolic enzyme catalyzing L-histidine catabolism by converting urocanic acid to imidazolonepropionate 1. The enzyme plays a role in hepatic metabolism and immune regulation. In non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC), UROC1 expression correlates with clinical outcomes and tumor immunity; decreased UROC1 expression associates with adverse HCC prognosis and altered tumor microenvironment composition 2. UROC1 also regulates hepatic detoxification pathways—luteolin enhances DEHP (environmental pollutant) clearance by degrading UROC1 protein and modulating the urocanic acid/UROC1 axis through ERK1/2 inhibition 3. Loss-of-function mutations in UROC1 cause urocanic aciduria, characterized by elevated urinary urocanic acid accumulation. Pathogenic variants (e.g., p.L70P disrupting N-terminal alpha-helices, p.R450C preventing substrate binding) abolish enzyme activity 1. While historically associated with intellectual disability, recent metabolomic studies demonstrate that UROC1 deficiency can present as a biochemically distinct but clinically benign phenotype in phenotypically normal individuals 4, suggesting developmental delay in urocanase-deficient patients warrants evaluation for alternative etiologies. UROC1 thus functions in histidine metabolism, hepatic homeostasis, and immune-oncologic processes.