PROZ encodes protein Z, a vitamin K-dependent plasma glycoprotein that primarily functions as an anticoagulant factor in hemostasis. The protein assists hemostasis by binding thrombin and promoting its association with phospholipid vesicles, while also inhibiting factor Xa activity in the presence of SERPINA10, calcium, and phospholipids 1. Loss-of-function variants in PROZ significantly increase the risk of noncardioembolic ischemic stroke (OR 2.34), confirming its anticoagulant role 1. Paradoxically, elevated circulating protein Z levels (>2.5 µg/ml) are also associated with increased cryptogenic stroke risk (OR 2.41), suggesting a complex non-linear relationship 2. Beyond coagulation, PROZ demonstrates diverse biological functions including regulation of amniotic fibroblast migration and proliferation during pregnancy 3, and its expression is epigenetically controlled by the scar-6 lncRNA locus, which maintains vascular homeostasis 4. Clinically, decreased PROZ levels are associated with prediabetes and type 2 diabetes 5, while low expression correlates with poor prognosis in hepatocellular carcinoma and affects sorafenib sensitivity 6. PROZ also shows potential as a urinary biomarker for Alzheimer's disease and mild cognitive impairment diagnosis 7.