F8 encodes coagulation factor VIII (FVIII), an X-linked gene essential for the intrinsic blood coagulation pathway. FVIII functions as a cofactor for factor IXa in converting factor X to its activated form (factor Xa), a critical step in thrombin generation. FVIII is synthesized in endothelial cells and circulates in plasma as part of a complex with von Willebrand factor. F8 mutations cause hemophilia A, the most common inherited coagulation disorder, with disease severity correlating with mutation type 1. Large deletions and nonsense mutations confer higher inhibitor development risk (3.6-fold and 1.4-fold increased odds, respectively), while missense mutations carry lower risk 1. Beyond classical F8 mutations, dysregulated microRNAs (hsa-miR-5581-3p and hsa-miR-542-3p) can suppress F8 expression and contribute to hemophilia A without detected F8 mutations 2. Conversely, F8 gene duplications cause elevated FVIII levels (Factor VIII Padua), representing a distinct thrombophilic defect associated with venous thromboembolism risk 3. F8 characterization has enabled comprehensive genetic diagnosis through targeted sequencing 45, carrier identification, prenatal diagnosis, and inhibitor development prediction 6. Gene therapy using recombinant adeno-associated viral vectors represents a promising therapeutic approach, offering potential for sustained, disease-altering correction of hemophilia A 7.