Heparin cofactor II (HCII; EC 3.4.21.xx) is a serine protease inhibitor (serpin) that inactivates thrombin rapidly in the presence of certain glycosaminoglycans (GAGs; dermatan sulfate, heparan sulfate, or heparin), but does not inhibit other proteases involved in coagulation or fibrinolysis. Heparin cofactor II has several biochemical properties that distinguish it from other serpins: it specifically inhibits thrombin, and the mechanism of inhibition involves binding of an acidic domain in HCII to thrombin exosite I. The rate of inhibition increases dramatically (more than 1000-fold) in the presence of heparin, heparan sulfate, or dermatan sulfate. HCII has been proposed to regulate coagulation or to participate in processes such as inflammation, atherosclerosis, and wound repair.