The transcription factor NF-κB has been extensively studied over the past two decades, with significant progress made in understanding its function and regulation. NF-κB plays a crucial role in various biological processes, particularly in the immune system, where it regulates the expression of cytokines, growth factors, and effector enzymes in response to multiple stimuli. The regulation of NF-κB signaling involves the classical and alternative pathways, which differ in their mechanisms and target genes. The classical pathway is activated by proinflammatory cytokines like TNFα, leading to the phosphorylation and degradation of IκB proteins, thereby releasing NF-κB to translocate to the nucleus. The alternative pathway, activated by stimuli such as LTβ and BAFF, involves the activation of IKKα and the phosphorylation of p100, leading to its processing into p52. The biological roles of NF-κB and IκB proteins are well-studied, with knockout mice providing insights into their functions in immune responses and apoptosis. The signaling pathways leading to NF-κB activation include TNFα, Toll/IL-1R, TCR, and BCR, each with distinct mechanisms involving adapter proteins and kinases. Understanding the complex regulation of NF-κB signaling is essential for comprehending its diverse roles in both normal and pathological conditions.The transcription factor NF-κB has been extensively studied over the past two decades, with significant progress made in understanding its function and regulation. NF-κB plays a crucial role in various biological processes, particularly in the immune system, where it regulates the expression of cytokines, growth factors, and effector enzymes in response to multiple stimuli. The regulation of NF-κB signaling involves the classical and alternative pathways, which differ in their mechanisms and target genes. The classical pathway is activated by proinflammatory cytokines like TNFα, leading to the phosphorylation and degradation of IκB proteins, thereby releasing NF-κB to translocate to the nucleus. The alternative pathway, activated by stimuli such as LTβ and BAFF, involves the activation of IKKα and the phosphorylation of p100, leading to its processing into p52. The biological roles of NF-κB and IκB proteins are well-studied, with knockout mice providing insights into their functions in immune responses and apoptosis. The signaling pathways leading to NF-κB activation include TNFα, Toll/IL-1R, TCR, and BCR, each with distinct mechanisms involving adapter proteins and kinases. Understanding the complex regulation of NF-κB signaling is essential for comprehending its diverse roles in both normal and pathological conditions.