Thrombomodulin (TM) is the cell surface receptor for thrombin. When occupied, thrombomodulin converts thrombin from a procoagulant protein into the activator of Protein C. Once activated Protein C (APC) has been generated, thrombomodulin acts as a major anticoagulant through its ability to inactivate various blood factors (Va, VΙΙΙa, Xa and XΙΙΙa). In competing for thrombin binding, thrombomodulin inhibits the proteolytic effect of thrombin in its clotting of fibrinogen, the inactivation of Protein S and the induction of platelet aggregation.

TM is an integral membrane glycoprotein resembling in structure the low-density lipoprotein (LDL) receptor.TM possesses several EGF repeats, of which numbers five and six are responsible for the high affinity binding of thrombin (Kd = 0.5 nM).