Preetpal Singh Sidhu. Journal of Pharmacy and Pharmacology 1 (2013) 1-10. Abstract: Thrombin is the most important and highly targeted protease in coagulation cascade to develop anticoagulation therapy. It has dual function in coagulation system and highly regulated by allosteric mode. Based on binding by various protein and peptides in exosite 1 and 2, it can act as pro-coagulant or anti-coagulant. The fine regulation of these two conflicting actions of thrombin is required to maintain the homeostasis. Besides exosites, binding of single sodium ion at sodium binding site can also modulate the dual action of thrombin. Various single point mutations can convert pro-coagulant to anti-coagulant thrombin and vice versa. Dual nature and allostery of thrombin makes it the most important regulator of coagulation cascade.