NF-κB p105/p50 is a crucial component of the NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling pathway. The NF-κB family in mammals includes members such as RelA (p65), RelB, c-Rel, NF-κB1 (p50/p105), and NF-κB2 (p52/p100), which regulate gene expression through the formation of various homodimers or heterodimers. NF-κB p105 serves as the precursor form of NF-κB1 and primarily exists in this form within the cell. In response to specific stimuli, such as proinflammatory cytokines, free radicals, ultraviolet radiation, and bacterial or viral infections, NF-κB p105 is cleaved by the proteasome into the p50 subunit. This cleavage process liberates NF-κB from its complex with the inhibitory protein IκB, enabling its translocation to the nucleus and activation of target gene transcription. NF-κB p50 (as well as p52) only contains the Rel homology domain (RHD) and lacks the transactivation domain (TD). Therefore, p50/p52 homodimers cannot activate gene transcription and instead function as inhibitory molecules. However, when they form heterodimers with RelA, RelB, or c-Rel, which possess the TD, they are able to bind to DNA and activate transcription. NF-κB p105/p50 plays a pivotal role in regulating various physiological processes, including immune responses, inflammation, cell growth, and death. Abnormal expression or dysfunction of these proteins is closely associated with the development and progression of multiple diseases, such as cancer, inflammatory bowel disease, and rheumatoid arthritis.