NFKBIB (NF-κB inhibitor beta) functions as a regulatory protein that controls NF-κB transcription factor activity through cytoplasmic sequestration 1. In unstimulated cells, NFKBIB binds NF-κB and masks its nuclear localization signal, preventing nuclear translocation 1. Upon cell stimulation, NFKBIB undergoes phosphorylation and degradation, releasing NF-κB to translocate to the nucleus where it activates transcription of immune and inflammatory response genes 1. Notably, newly synthesized unphosphorylated NFKBIB can rebind NF-κB and protect it from further inactivation, allowing nuclear NF-κB function 1. Association with NKIRAS proteins increases NFKBIB resistance to degradation, prolonging its inhibitory effects. NFKBIB dysfunction contributes to multiple disease pathologies. Dysregulation is implicated in inflammatory conditions, where elevated NF-κB signaling drives myeloid bias and inflammatory responses 2. In gastrointestinal stromal tumors, nuclear KIT drives NFKBIB expression, creating an autoregulatory loop that maintains KIT expression and imatinib resistance 3. In gastric cancer, miR-20a-mediated NFKBIB downregulation enhances NF-κB activation and promotes chemoresistance through upregulation of anti-apoptotic factors 4. NFKBIB upregulation has been identified as a hub gene in dilated cardiomyopathy 5 and in cytokine storm-related inflammatory diseases 6, suggesting its role in pathological inflammation.