Protein Z (PZ) is a vitamin K-dependent glycoprotein produced in the liver. The concentration of PZ in plasma is ~3 micrograms/milliliters (~48 nM) where it circulates in complex with protein Z-dependent protease inhibitor (ZPI). In the presence of calcium and negatively charged phospholipid, PZ acts as a cofactor in the inhibition of activated factor X (FXa) by ZPI. Protein Z is expressed as a single chain molecule with a molecular weight of 62 kDa. The structure of PZ is similar to many other vitamin-K dependent coagulation proteins, consisting of an N-terminal calcium-binding domain followed by EGFlike domains and a C-terminal pseudo-catalytic domain. Unlike most other vitamin K-dependent coagulation factors, the catalytic-like domain does not contain the usual catalytic triad of a pro-enzyme and does not demonstrate any enzymatic activity.

The function of PZ in vivo has yet to be elucidated, but evidence suggests that the cofactor function of PZ is dependent on its ability to bind the PZ-ZPI complex to a phospholipid surface where it can interact with FXa. This cofactor activity of PZ is regulated during coagulation through proteolysis by the enzymes FXa and activated factor XI. Reduced levels of plasma PZ are observed in warfarin therapy, and in patients with disseminated intravascular coagulation (DIC). Patients diagnosed with PZ-deficiency have been reported to exhibit abnormal bleeding after surgery, yet paradoxically, low plasma concentrations of PZ have been shown to increase the risk of thromboembolic events when associated with Factor V-Leiden mutation.