Lorenzini T, Fliegauf M, Klammer N, et al. - Since a rising number of NFKB1 variants are being found in patients with heterogeneous immunologic phenotypes, so researchers characterized the clinical as well as cellular phenotype and the treatment of patients carrying heterozygous NFKB1 mutations. They assessed 231 people having 105 distinct heterozygous NFKB1 variants. Of 105 distinct NFKB1 variants in 157 persons from 68 unrelated families, 56 were classified as pathogenic. Experts noted incomplete clinical penetrance (70%) as well as age-dependent severity of NFKB1-associated phenotypes. NF-κB1–related disease was identified as an inborn error of immunity characterized by immune dysregulation, rather than a mere primary immunodeficiency. Immunoglobulin replacement and immunosuppressive agents are current treatment options. This work affords a comprehensive clinical overview of the NF-κB1–related phenotype, which incorporates immunodeficiency, autoimmunity, autoinflammation, and cancer. There is a necessity to spread awareness among clinicians from each and every medical discipline about this autosomal-dominant disease because this entity shows multisystem involvement. Considering hematopoietic stem cell transplantation and NF-κB1 pathway–targeted treatment strategies in the future was recommended.