Factor IX (F9) is a vitamin K-dependent plasma protein that functions as a critical component of the intrinsic blood coagulation pathway 1. The protein participates in converting factor X to its active form in the presence of calcium ions, phospholipids, and factor VIIIa, serving as an essential serine endopeptidase in the coagulation cascade 1. F9 gene mutations are the primary cause of hemophilia B, an X-linked bleeding disorder 12. Complete F9 gene deletions result in severe hemophilia B with factor IX activities below 1%, while duplications and triplications can lead to elevated factor IX levels and potential thrombotic phenotypes 3. The gene shows extensive genetic variability, with over 1,900 unique variants identified, including 431 F9-specific variants, many of which are novel 1. Genotyping is clinically important for molecular confirmation of hemophilia B, carrier testing, and identifying patients at risk for inhibitor formation, particularly those with large deletions 2. Interestingly, F9 expression appears downregulated in hepatocellular carcinoma, where reduced expression correlates with adverse outcomes and advanced disease stages 4. The gene represents a target for emerging gene therapy approaches using CRISPR/Cas9 technology for hemophilia B treatment 5.