NFKB1 encodes the p50 subunit of the nuclear factor kappa-B transcription factor complex, which associates with RELA/p65 to form the NF-κB p65-p50 heterodimer 12. This complex binds kappa-B consensus sequences in gene enhancer regions to regulate transcription of immune response and acute phase reaction genes 12. NFKB1 is essential for natural killer (NK) cell maturation and effector functions; mutations impair NK cell cytotoxicity and interferon-gamma production 3. NFKB1 also functions as a transcriptional regulator of CD200R1, controlling microglial quiescence and neuroinflammation 4. Loss-of-function NFKB1 mutations cause autosomal-dominant inborn errors of immunity characterized by immunodeficiency with immune dysregulation 5. Patients present with hypogammaglobulinemia (88.9%), reduced switched memory B cells, and respiratory infections, alongside autoimmunity (57.4%), lymphoproliferation (52.4%), and autoinflammation (29.6%) 5. Truncating variants impair autophagy and trigger combined NLRP3 inflammasome and type I interferon activation, predisposing to necrotizing fasciitis 6. Reduced NFKB1 expression contributes to Parkinson's disease pathogenesis through CD200R1 dysregulation and microglial overactivation 4. Additionally, NFKB1 rs28362491 polymorphism associates with decreased head and neck cancer risk, particularly nasopharyngeal carcinoma 7.