SERPINC1 encodes antithrombin III (ATIII), the most important serine protease inhibitor regulating blood coagulation 1. ATIII inhibits multiple coagulation proteases including thrombin, factors IXa, Xa, and XIa, with activity greatly enhanced by heparin binding 2. Beyond anticoagulation, ATIII exhibits anti-inflammatory effects through coagulation-dependent and independent mechanisms 1. Diseases associated with SERPINC1 dysfunction include hereditary antithrombin deficiency, a rare autosomal-dominant disorder (1:2,000-3,000 prevalence) causing recurrent venous thromboembolism 3. Approximately 80% of antithrombin deficiency cases involve SERPINC1 mutations, predominantly point mutations or small indels affecting the 7 exons 4. Disease-causing SERPINC1 variants confer comparable thrombotic risk to factor V Leiden and prothrombin G20210A variants, with hazard ratios of 1.6 for heterozygous carriers; risk increases to 3.9 with multiple thrombophilia variants 5. Truncating mutations impair protein secretion despite normal mRNA expression 6, while missense variants may disrupt glycosylation sites affecting function 3. Emerging therapeutic approaches include RNAi-mediated antithrombin reduction for hemophilia 7 and CRISPR-corrected iPSC-derived hepatocytes for hereditary deficiency 8. Approximately 10-15% of antithrombin deficiency cases remain unexplained, suggesting additional genetic mechanisms 4.