Nfkbiz, encoding IκB-ζ protein, is a member of the nuclear factor kappa B inhibitory family. It plays a crucial role in regulating the NF-κB signaling pathway, which is involved in various biological processes such as inflammation, cell proliferation, and survival [2,3].

In ulcerative colitis, mutations in Nfkbiz are highly prevalent in the epithelium. These mutant cells seem to be selected against during colorectal carcinogenesis as Nfkbiz-mutant mice show attenuated tumour formation, indicating a negative selection of Nfkbiz-mutant cells in colorectal cancer development [1].

In hepatocellular carcinoma, downregulation of Nfkbiz is observed. Overexpression of Nfkbiz in HCC cells inhibits their growth and metastasis in vivo, suggesting Nfkbiz suppresses HCC tumorigenesis and metastasis by regulating NFκB signaling transduction [2].

In bladder cancer, NFKBIZ expression is low, and it inhibits the proliferation of bladder cancer cells through the PTEN/PI3K/Akt signaling pathway [3].

In conclusion, Nfkbiz is essential in regulating the NF-κB signaling pathway, influencing biological processes related to inflammation, cell proliferation, and survival. Studies using gene-knockout mouse models have revealed its significance in diseases like ulcerative colitis, hepatocellular carcinoma, and bladder cancer, providing insights into disease mechanisms and potential therapeutic targets.