Thrombomodulin.

Since its discovery as a critical cofactor in the initiation of the protein C (PC) anticoagulant pathway [1,2], biochemical and structural investigations, combined with in vivo analyses of genetically engineered mice have revealed new, and in part PC- and thrombin-independent aspects of thrombomodulin (TM) function in fibrinolysis and inflammation, and in embryogenesis. This review summarizes more recent structural and functional investigations of TM, gives an overview of the association of TM gene polymorphisms with human disease, and provides a synopsis of what is know about TM function in disease states of thrombosis, stroke, arteriosclerosis, and cancer. Newly emerging aspects of TM function in inflammation and embryogenesis are presented and discussed in detail.