RELA, also known as NF-κB p65, is a subunit of nuclear factor kappa B (NF-κB), a transcription factor involved in various biological processes, including immune response, inflammation, cell survival, and proliferation. The NF-κB pathway is a key signaling cascade that plays a crucial role in regulating the expression of genes involved in these processes [3,5,7,8,9].

In silica-induced pulmonary fibrosis, RELA-mediated upregulation of LINC03047 promotes ferroptosis and epithelial-mesenchymal transition (EMT) via SLC39A14, suggesting its role in the progression of silicosis [1]. In supratentorial ependymoma, the C11orf95-RELA fusion protein modulates chromatin states and mediates chromatin interactions, leading to transcriptional reprogramming [2]. In hypopharyngeal cancer, RELA is required for CD271 expression and stem-like characteristics [3]. In human T cells, RELA tunes innate-like interferon I/III responses [4]. In oral squamous cell carcinoma, RELA promotes tumor progression via the TFAP2A-Wnt/β-catenin signaling pathway [5]. In cancer cells, mitochondrial RelA promotes mtDNA G-quadruplex formation for hypoxia adaptation [6]. WSB1/2 target chromatin-bound lysine-methylated RelA for proteasomal degradation and NF-κB termination [7]. In pancreatic cancer, NF-κB/RelA controlled A20 limits TRAIL-induced apoptosis [8]. The C11orf95-RELA fusion drives aberrant gene expression through unique epigenetic regulation for ependymoma formation [9].

In conclusion, RELA is a crucial component of the NF-κB pathway, playing important roles in multiple biological processes and disease conditions such as fibrosis, various cancers, and immune-related responses. Studies using different models, though not specifically KO/CKO mouse models in the provided references, have revealed its diverse functions in these contexts, contributing to our understanding of disease mechanisms and potential therapeutic targets.