Antithrombin (AT; formerly antithrombin III, ATIII), encoded by the SERPINC1 gene on chromosome 1q25, is a plasma serine protease inhibitor of the serpin superfamily and the most important endogenous anticoagulant. It is synthesized by hepatocytes and circulates in blood plasma. Its primary targets are the activated coagulation serine proteases thrombin (factor IIa) and factor Xa, and to a lesser extent factors IXa, XIa, XIIa, and VIIa; by a suicide-substrate mechanism it forms irreversible 1:1 complexes with these enzymes, directly damping the blood coagulation cascade and limiting clot formation. Antithrombin contains an N-terminal heparin-binding domain and a C-terminal reactive-center loop; binding of heparin (or heparan sulfate on the endothelial surface) produces a rapid, up to ~1000-fold acceleration of its inhibitory activity against thrombin and factor Xa, which is the molecular basis of heparin anticoagulation therapy. Beyond anticoagulation, antithrombin has anti-inflammatory and anti-vascular-permeability effects, and hereditary antithrombin deficiency markedly increases venous thromboembolism risk. Antithrombin is a soluble plasma protein acting in the circulation and at the endothelial surface.