CFB (Complement Factor B) is a serine protease essential for activation of the alternative complement pathway 1. As a key component of the C3 convertase, CFB is cleaved upon C3b binding to generate active fragments that amplify complement cascade activation and drive opsonization and phagocytosis of pathogens 1. Beyond canonical extracellular functions, CFB participates in intracellular complement signaling within fibroblasts, where it contributes to metabolic reprogramming and proinflammatory mediator production 2. CFB variants have significant disease associations. Loss-of-function mutations, particularly the rs4151651 G252S polymorphism, impair CFB cleavage and reduce complement-mediated phagocytosis, increasing susceptibility to perianal Crohn's disease 1. Conversely, protective CFB/C2 gene variants (rs9332739, rs547154, rs4151667, rs641153) demonstrate strong protective effects against age-related macular degeneration, reducing disease risk by approximately 50% in carriers of rare alleles, with stronger protection observed in Caucasian populations 3. The clinical significance of CFB is underscored by its role as a therapeutic target in complement-driven pathologies. Understanding CFB function and genetics provides insights into both autoinflammatory diseases and age-related degenerative conditions, supporting development of complement-targeted interventions.