Nuclear Factor kappa B (NF-kB) is a transcription factor that plays a key role in regulating various physiological and pathological processes, including inflammation, immune response, cell proliferation, survival, and apoptosis. NF-kB is actually a family of related transcription factors that form dimers, including p65 (RelA), p50, p52, RelB, and c-Rel. These proteins can combine in different ways to form active NF-kB complexes. The NF-κB signaling pathway includes both canonical and non-canonical routes. The canonical NF-κB pathway responds rapidly to various stimuli, leading to short-term transcriptional activity that regulates proinflammatory gene expression and mediates the inflammatory response. In contrast, the non-canonical NF-κB pathway is activated through certain TNF receptor superfamily members and involves protein synthesis, resulting in slower but sustained activation. This pathway plays a crucial role in immune cell development, lymphoid organ formation, immune homeostasis, and immune response. Both pathways are regulated with precision, emphasizing the importance of ubiquitination in their function. Recent research shows that abnormal NF-κB activity is linked to inflammation-related diseases and cancers, making NF-κB a potential target for therapeutic interventions.