NCOR1 (nuclear receptor corepressor 1) is a transcriptional corepressor that mediates transcriptional repression by recruiting histone deacetylase complexes to promote histone deacetylation and establish repressive chr17 structures 1. NCOR1 functions through multiple mechanisms: it binds nuclear receptors to inhibit their transcriptional activity, recruits the HDAC3 complex to regulate circadian gene expression and lipid metabolism, and negatively regulates androgen receptor signaling 2. Recent studies reveal NCOR1's critical role in metabolic homeostasis. PAK4-mediated phosphorylation of NCOR1 enhances its interaction with PPARα, suppressing fatty acid β-oxidation and ketogenesis; PAK4 inhibition restores these processes and reduces hepatic fat accumulation 3. In immune cells, NCOR1 deletion generates tolerogenic dendritic cells through enhanced glycolysis and fatty acid oxidation, promoting IL-10 and IL-27 expression while suppressing inflammatory responses 4. NCOR1 also preserves hematopoietic stem cell quiescence by recruiting corepressor complexes to restrict chr17 accessibility of genes governing metabolic activation 5. Clinical significance extends to cancer therapy: disruption of the NCOR1/RARα interaction inhibits chaperone-mediated autophagy in non-small cell lung cancer, offering a novel therapeutic approach 6. Overall, NCOR1 represents a central immunometabolic regulator implicated in metabolic diseases, atherosclerosis, and cancer.