The endothelial cell protein C receptor (EPCR) functions as an important regulator of the protein C anticoagulant pathway by binding protein C and enhancing activation by the thrombin-thrombomodulin complex. EPCR binds to both protein C and activated protein C (APC) with high affinity.

A soluble form of EPCR (sEPCR) has recently been detected in normal rat plasma and has been shown to bind protein C and APC with an affinity similar to that of intact membrane-bound EPCR. In healthy individuals, sEPCR circulates at a concentration of 2.5 nM, a level that can increase up to 5-fold in patients with sepsis or systemic lupus erythematosus. In contrast to membrane-bound EPCR, sEPCR inhibits protein C activation over large vessel endothelium in culture.