Prekallikrein (PK), previously known as Fletcher Factor, is a single chain glycoprotein produced in the liver. The plasma concentration of PK is 50ug/ml (550nM), approximately 75% of which circulates in complex with high molecular weight kininogen (HK) and the remainder as free PK. Plasma PK is heterogeneous in both mass and charge due to variable degrees of glycosylation. Approximately 90% of plasma PK has an apparent molecular weight of 88kD as determined by SDS-PAGE and the remaining 10% has an apparent mass of 85kD. The catalytic site resides in the light chain. The heavy chain of PK contains four appledomain structures similar to those found in FXI and these are required for binding of PK to HK. PK is the zymogen form of the enzyme kallikrein, which is involved in the proteolysis of kininogens with subsequent release of bradykinin, a potent vasodilator. PK participates in the contact phase of coagulation as a substrate for surface-bound activated factor XII (FXIIa) in the presence of the cofactor HK. As PK and factor XI (FXI) both circulate in complex with HK, both are localized to activating surfaces through their respective binding to HK. Limited proteolysis of PK by FXIIa generates kallikrein, a two-chain serine protease that initiates the reciprocal activation of PK and FXI.Kallikrein activity in plasma is regulated predominantly by C1- Inhibitor and a2macroglobulin, with relatively minor contributions by Protein C Inhibitor, a2antiplasmin, and antithrombin.