NFKB1, encoding the p105/p50 subunits of NF-κB, is a key transcription factor. The NF-κB signaling pathway, in which NFKB1 is involved, governs crucial cellular processes such as immune responses, apoptosis, and cellular homeostasis [2,5]. Aberrant activation of this pathway is associated with carcinogenesis [2].

NFKB1-related disease, often caused by heterozygous NFKB1 mutations, presents as an inborn error of immunity with immune dysregulation rather than a simple primary immunodeficiency. Clinical features include hypogammaglobulinemia, reduced switched memory B cells, respiratory and gastrointestinal infections, as well as high frequencies of autoimmunity, lymphoproliferation, non-infectious enteropathy, opportunistic infections, autoinflammation, and malignancy [1]. Truncating monoallelic loss-of-function variants of NFKB1 can lead to combined NLRP3 inflammasome activation and type I interferon signaling, predisposing patients to necrotizing fasciitis [3]. In addition, the NFKB1-94ins/delATTG polymorphism is associated with a decreased risk of overall cancer, and this association holds for some specific cancers like lung, nasopharyngeal, prostate, ovarian, and oral squamous cell carcinoma [4].

In conclusion, NFKB1 is vital for normal immune function and maintaining cellular homeostasis. Studies on NFKB1-related mutations in patients and animal models have revealed its complex roles in immunodeficiency, autoimmunity, autoinflammation, and cancer. Understanding NFKB1 is crucial for developing therapeutic strategies for these related diseases.