Rel, a member of the Rel/NF-κB transcription factor family, shares sequence homology within the rel domain. NF-κB pathways are crucial in regulating a wide variety of genes, especially those related to the immune system's function. In normal physiology, c-Rel, a specific member of the Rel family, has high expression in the hematopoietic lineage, and its expression and activation can be triggered by diverse stimuli [1,2].

Gene knockout studies have provided insights into c-Rel's functions. In hepatocellular carcinoma (HCC), global (Rel-/-) and epithelial specific (RelAlb) c-Rel knockout mice develop more tumors with higher proliferative rates and increased DNA damage compared to wild-type controls, indicating c-Rel signaling is important for preventing HCC initiation after genotoxic injury [3]. In c-Rel-deficient (c-Rel-/-) mice, there is a significantly reduced response to papain-and IL-33-induced lung inflammation, as c-Rel is critical for the function of group 2 innate lymphoid cells (ILC2s) in the lung [4]. Also, c-Rel deficiency protected mice from imiquimod-induced psoriasis-like lesions, specifically compromising TLR7-induced inflammation in dendritic cells [5].

In conclusion, c-Rel is a key regulator in multiple biological processes and diseases. Gene knockout mouse models have revealed its roles in tumorigenesis, such as in HCC, and in immune-related conditions like lung inflammation and psoriasis. These findings contribute to understanding the underlying mechanisms and may potentially guide the development of targeted therapies.