VKORC1 (vitamin K epoxide reductase complex subunit 1) is the catalytic subunit of the vitamin K epoxide reductase complex, which catalyzes the reduction of inactive vitamin K 2,3-epoxide to active vitamin K in the endoplasmic reticulum membrane. This enzymatic activity is essential for vitamin K-dependent protein gamma-carboxylation, enabling the activation of clotting factors required for normal blood coagulation and bone development 1. VKORC1 is the primary target of warfarin and other coumarin anticoagulants, which inhibit its enzymatic activity to reduce vitamin K recycling and suppress coagulation factor synthesis 2. VKORC1 genetic polymorphisms, particularly at positions -1639G>A and 1173C>T, strongly influence warfarin dose requirements and therapeutic response across diverse populations 34. Patients carrying VKORC1 variant alleles require significantly lower warfarin maintenance doses (26-50% reduction) compared to wild-type carriers 5. VKORC1 polymorphisms also associate with adverse events including overanticoagulation and bleeding risk during warfarin therapy 3. Clinically, VKORC1 genotyping can guide personalized warfarin dosing to improve safety and therapeutic efficacy, though current evidence supports genetic testing primarily in populations of European ancestry where data are most robust 6. Rare hereditary VKORC1 mutations cause warfarin resistance, defined as requiring >70 mg weekly to maintain therapeutic anticoagulation 72.