The NF-κB family of transcription factors plays a critical role in inflammation, immunity, cell proliferation, differentiation, and survival. NF-κB activation depends on the phosphorylation-induced degradation of inhibitory IκB proteins, which are retained by NF-κB dimers in the cytosol. The IκB kinase (IKK) complex is essential for IκB phosphorylation and signal transduction to NF-κB. Post-translational modifications of IκB and NF-κB proteins further regulate NF-κB activity. NF-κB signaling pathways converge on the IKK complex, which phosphorylates IκBs, leading to their ubiquitination and degradation by the proteasome. This process releases NF-κB dimers, which translocate to the nucleus and activate target genes. The NF-κB pathway is regulated by various stimuli, including bacterial and viral infections, inflammatory cytokines, and antigen receptor engagement, and its dysregulation is implicated in diseases such as arthritis, immunodeficiency, autoimmunity, and cancer. The NF-κB family consists of five proteins that form distinct homo- and heterodimers, with p65 (RelA), RelB, c-Rel, p105/p50 (NF-κB1), and p100/52 (NF-κB2) being the major components. These dimers are regulated by post-translational modifications, including phosphorylation, ubiquitination, and acetylation, which fine-tune their activity. The termination of the NF-κB response involves the resynthesis of IκB proteins and the degradation of NF-κB dimers through mechanisms such as ubiquitination and proteasomal degradation. Understanding the complex regulatory networks of the NF-κB pathway is crucial for developing targeted therapies for various diseases.The NF-κB family of transcription factors plays a critical role in inflammation, immunity, cell proliferation, differentiation, and survival. NF-κB activation depends on the phosphorylation-induced degradation of inhibitory IκB proteins, which are retained by NF-κB dimers in the cytosol. The IκB kinase (IKK) complex is essential for IκB phosphorylation and signal transduction to NF-κB. Post-translational modifications of IκB and NF-κB proteins further regulate NF-κB activity. NF-κB signaling pathways converge on the IKK complex, which phosphorylates IκBs, leading to their ubiquitination and degradation by the proteasome. This process releases NF-κB dimers, which translocate to the nucleus and activate target genes. The NF-κB pathway is regulated by various stimuli, including bacterial and viral infections, inflammatory cytokines, and antigen receptor engagement, and its dysregulation is implicated in diseases such as arthritis, immunodeficiency, autoimmunity, and cancer. The NF-κB family consists of five proteins that form distinct homo- and heterodimers, with p65 (RelA), RelB, c-Rel, p105/p50 (NF-κB1), and p100/52 (NF-κB2) being the major components. These dimers are regulated by post-translational modifications, including phosphorylation, ubiquitination, and acetylation, which fine-tune their activity. The termination of the NF-κB response involves the resynthesis of IκB proteins and the degradation of NF-κB dimers through mechanisms such as ubiquitination and proteasomal degradation. Understanding the complex regulatory networks of the NF-κB pathway is crucial for developing targeted therapies for various diseases.