Rela, also known as p65, is one of the most critical and extensively studied members of the nuclear factor κB (NF-κB) transcription factor family. As the core executor of the NF-κB signaling pathway, it typically forms the canonical p65-p50 heterodimer with the p50 subunit. In the resting state, Rela is anchored in the cytoplasm by the IκB inhibitory protein. Once the cell receives external stimuli such as inflammatory cytokines (TNF-α, IL-1), pathogen-associated molecular patterns (PAMPs), or stress signals, the IκB kinase (IKK) complex is activated, leading to the degradation of IκB and the release of Rela/p65. The activated Rela rapidly translocates to the nucleus, initiating the transcription of a large number of target genes that are widely involved in key biological processes such as acute inflammatory responses, cell survival, proliferation, and differentiation. Therefore, Rela serves as the core hub connecting upstream signals with downstream gene expression and plays a crucial role in immune responses, inflammatory diseases, and cancer.