GGCX (gamma-glutamyl carboxylase) is a vitamin K-dependent enzyme that catalyzes the post-translational carboxylation of glutamate residues to gamma-carboxyglutamate (Gla) residues in multiple substrate proteins 1. The enzyme couples this carboxylation with concurrent oxidation of vitamin K hydroquinone to vitamin K epoxide, with both reactions occurring in the same active site 1. Structurally, GGCX is a transmembrane protein whose propeptide-binding domain stabilizes critical transmembrane helices to create the vitamin K-binding pocket, and cholesterol interactions regulate its cellular protein levels 1. GGCX catalyzes gamma-carboxylation of essential coagulation factors (F2, F7, F9, F10) and anticoagulants like protein C, which are critical for hemostasis 2. The enzyme also carboxylates osteocalcin for bone metabolism and matrix Gla protein for calcium homeostasis 1. Notably, GGCX can undergo membrane topology inversion to carboxylate the antiviral signaling protein MAVS in the cytoplasm, enhancing antiviral interferon responses 3. Clinically, GGCX mutations cause combined vitamin K-dependent clotting factor deficiency (VKCFD1) with variable penetrance and pleiotrophic manifestations affecting skin, eye, cardiac, and bone tissues 4. GGCX variants are associated with pulmonary arterial hypertension with moderate evidence 5, accounting for approximately 0.9% of idiopathic PAH cases 6. GGCX polymorphisms show minimal impact on warfarin dosing compared to VKORC1 variants 7.