NFKBIA encodes IκBα, a critical negative regulator of NF-κB signaling that inhibits dimeric NF-κB/REL complexes by masking their nuclear localization signals and sequestering them in the cytoplasm 1. Upon inflammatory stimulation, IκBα becomes phosphorylated, triggering ubiquitination and degradation, which permits NF-κB translocation to the nucleus for transcription activation 2. NFKBIA plays a central role in immune homeostasis and inflammatory disease prevention by controlling NF-κB-dependent expression of immune response genes 3. Genetic variants in NFKBIA associate with cancer susceptibility and inflammatory diseases. The rs3138053 polymorphism increases cancer risk overall, particularly hepatocarcinoma susceptibility, while rs696 exhibits protective effects against Hodgkin lymphoma and overall tumorigenesis 4. The -826C/T polymorphism associates with autoimmune and inflammatory disease development 5. In gliomas, reduced NFKBIA expression correlates with advanced tumor grade and poorer overall survival, positioning it as an independent prognostic biomarker 6. NFKBIA mutations cause ectodermal dysplasia and immunodeficiency 2, highlighting its essential role in immune function. These findings establish NFKBIA as both a fundamental regulator of immune homeostasis and a potential therapeutic target across inflammatory, autoimmune, and malignant diseases.