CPB2 encodes carboxypeptidase B2 (also called thrombin-activatable fibrinolysis inhibitor, TAFI), a hepatically secreted zymogen that functions as a potent regulator of fibrinolysis and inflammation 1. Upon activation by thrombin-thrombomodulin or plasmin, CPB2 cleaves C-terminal basic residues (arginine or lysine) from biologically active peptides, including kinins and anaphylatoxins, thereby regulating their activities 1. Critically, CPB2 down-regulates fibrinolysis by removing C-terminal lysine residues from partially degraded fibrin, forming a molecular link between coagulation and fibrinolysis 2. Genetic variation in CPB2 is clinically significant; the Ala147Thr variant shows sex-specific protection against venous thrombosis in females but not males 3, while the Thr325Ile polymorphism may influence thrombotic predisposition 1. CPB2 variants in the exon 6-7 region are maintained by balancing selection and exhibit haplotype-preferential splicing, suggesting functional importance of alternative isoforms 2. Sex steroid hormones (estrogen and progesterone) decrease CPB2 expression and plasma TAFI levels through indirect signaling mechanisms, providing molecular explanation for altered thrombotic risk with hormone therapy 4. Elevated CPB2 activity contributes to impaired fibrinolysis in immune thrombocytopenia patients, correlating with increased thrombotic risk 5.