Ncor1, also known as Nuclear receptor corepressor 1, is a transcriptional corepressor that links chromatin-modifying enzymes with gene-specific transcription factors. It plays a crucial role in multiple biological processes such as immune regulation, metabolism, and cell development. It is involved in pathways like glycolysis, fatty acid oxidation, and Notch signaling, and is important for maintaining the homeostasis of various cell types [2,4,6]. Genetic models, especially knockout (KO) and conditional knockout (CKO) mouse models, have been instrumental in studying its functions.

In dendritic cells, Ncor1 ablation generates immune-tolerant DCs through enhanced IL-10, IL-27 and SOCS3 expression, and these tolerogenic DCs rely on enhanced glycolysis and fatty acid oxidation-driven oxygen consumption [1]. In vascular smooth muscle cells, smooth muscle Ncor1 deficiency leads to a switch from contractile to degradative phenotype, increasing the incidence of aortic aneurysms [3]. In myeloid cells, Ncor1 depletion exacerbates Mycobacterium tuberculosis growth by dysregulating the AMPK-mTOR-TFEB axis [7]. In osteoclastogenesis, Ncor1 deficiency promotes osteoclast and neutrophil formation and exacerbates periodontitis [5].

In conclusion, Ncor1 is essential for maintaining immune tolerance, cell-type homeostasis, and controlling pathogen growth. KO/CKO mouse models have revealed its roles in diseases such as aortic aneurysm, periodontitis, and Mycobacterium tuberculosis infection, providing insights into potential therapeutic targets for these conditions.