NFKB2 encodes a transcription factor subunit that functions in both canonical and non-canonical NF-κB signaling pathways, playing crucial roles in immune regulation and disease pathogenesis. The protein exists primarily as p100, which undergoes proteolytic processing to generate the active p52 subunit 1. NFKB2 deficiency causes common variable immunodeficiency-10, with patients exhibiting increased susceptibility to viral infections, autoimmune disorders, ectodermal dysplasia, and pituitary involvement compared to NFKB1 deficiency patients 1. Functionally, NFKB2 deficiency impairs the development of AIRE-expressing medullary thymic epithelial cells, leading to production of neutralizing autoantibodies against type I interferons and predisposition to severe viral diseases including life-threatening COVID-19 pneumonia 2. In cancer contexts, NFKB2 promotes tumor progression through multiple mechanisms: it regulates melanoma growth via the BRD4/NFKB2/SPP1 pathway 3, facilitates immune evasion in colorectal cancer by promoting CD8+ T-cell exhaustion through the NFKB2-STAT2/PD-L1 axis 4, and contributes to pancreatic cancer metastasis when overexpressed 5. Additionally, NFKB2 serves as a specific transcription factor in rheumatoid arthritis synovial macrophages 6 and shows elevated expression in sudden sensorineural hearing loss patients, suggesting inflammatory involvement 7.