HABP2 encodes a serine protease that binds hyaluronan and participates in coagulation and fibrinolysis pathways. The protein cleaves fibrinogen's alpha and beta chains but does not initiate fibrin clot formation directly, and converts inactive pro-urokinase to its active form while activating coagulation factor VII. It may function as a tumor suppressor negatively regulating cell proliferation and migration. HABP2 has emerged as a biomarker and therapeutic target in multiple disease contexts. In hepatocellular carcinoma, serum HABP2 levels as part of a protein panel (P4: HABP2, CD163, AFP, PIVKA-II) distinguished HCC from liver cirrhosis and healthy controls with high accuracy and predicted HCC development median 11.4 months before imaging 1. In lung cancer, HABP2 overexpression increased tumor growth ~2-fold and lung metastasis ~10-fold in xenograft models, with increased expression observed in patient non-small cell lung cancer samples 2. HABP2 is also implicated in early-onset ischemic stroke: genetic variants near HABP2 reached genome-wide significance and correlated with plasma factor VII-activating protease levels 3, and elevated FSAP (the HABP2 protein product) in stroke patients with poor collateral circulation was reversed by high-molecular-weight hyaluronan treatment 4. Regarding familial nonmedullary thyroid cancer, evidence for the HABP2 G534E variant as a causative mutation is conflicting: while it was identified in multiple kindreds 5, larger population studies found the variant did not segregate with disease and showed no association with thyroid cancer risk 67.