HABP2 encodes a plasma serine protease with multifaceted roles in coagulation and cancer biology. Functionally, HABP2 cleaves fibrinogen alpha and beta chains but does not initiate fibrin clot formation or fibrinolysis 1. Notably, it converts inactive pro-urokinase to active urokinase plasminogen activator (uPA) 21, and genetic variants show association with factor VII-activating protease levels, implicating HABP2 in coagulation pathways 3. In cancer, HABP2 demonstrates opposing roles: HABP2 G534E mutations segregate with familial nonmedullary thyroid cancer (FNMTC) in approximately 14% of kindreds 4, though segregation analysis suggests incomplete penetrance 5. Conversely, HABP2 overexpression promotes lung cancer progression through enhanced uPA activation, increasing tumor growth ~2-fold and metastasis ~10-fold in xenografts 6. As a circulating biomarker, HABP2 appears in diagnostic panels for hepatocellular carcinoma (HCC) early detection, distinguishing HCC from cirrhosis with 97.5% sensitivity and predicting HCC conversion 11.4 months pre-imaging 7. In acute ischemic stroke, elevated FSAP (HABP2 product) correlates with poor collateral status; high-molecular-weight hyaluronan inhibition of FSAP improves endothelial function via Wnt signaling 8. These findings suggest HABP2 functions contextually as both tumor suppressor and promoter depending on cancer type and tissue microenvironment.