The article provides a comprehensive overview of the Rel/NF-κB family of transcription factors and their regulatory mechanisms, particularly focusing on the role of IκB proteins. NF-κB proteins are sequestered in the cytoplasm by IκB proteins, which mask their nuclear localization signal (NLS). Upon stimulation, NF-κB is released from IκB and translocates to the nucleus to regulate gene transcription. The activation of NF-κB does not require protein synthesis, allowing rapid and efficient gene activation. This system is crucial for immune, inflammatory, and acute phase responses. The article also discusses the regulation of NF-κB by various signals, including cytokines, bacterial lipopolysaccharide (LPS), and viral proteins. It highlights the importance of IκB phosphorylation and degradation in NF-κB activation, with specific attention to the phosphorylation of IκBα at Ser-32 and Ser-36 residues and its subsequent degradation by the 26S proteasome. The article concludes by emphasizing the widespread distribution and diverse functions of the Rel/NF-κB/IκB system in cellular processes, including cell proliferation, apoptosis, and immune responses.The article provides a comprehensive overview of the Rel/NF-κB family of transcription factors and their regulatory mechanisms, particularly focusing on the role of IκB proteins. NF-κB proteins are sequestered in the cytoplasm by IκB proteins, which mask their nuclear localization signal (NLS). Upon stimulation, NF-κB is released from IκB and translocates to the nucleus to regulate gene transcription. The activation of NF-κB does not require protein synthesis, allowing rapid and efficient gene activation. This system is crucial for immune, inflammatory, and acute phase responses. The article also discusses the regulation of NF-κB by various signals, including cytokines, bacterial lipopolysaccharide (LPS), and viral proteins. It highlights the importance of IκB phosphorylation and degradation in NF-κB activation, with specific attention to the phosphorylation of IκBα at Ser-32 and Ser-36 residues and its subsequent degradation by the 26S proteasome. The article concludes by emphasizing the widespread distribution and diverse functions of the Rel/NF-κB/IκB system in cellular processes, including cell proliferation, apoptosis, and immune responses.