CTBP1 (C-terminal binding protein 1) is a transcriptional corepressor with dual enzymatic and regulatory functions. Structurally, CTBP1 functions as an NADH-sensitive oligomerization-dependent corepressor that forms tetramers to enhance histone methyltransferase G9a activity, promoting H3K9me2-mediated transcriptional repression 1. CTBP1 represses diverse genes including inflammasome components through interaction with transcription factors like FOXP1 2 and suppresses aromatase expression in granulosa cells 3. Its dehydrogenase activity links metabolic state to gene regulation via NADH-dependent oligomerization 2. Clinically, CTBP1 mutations cause hypotonia, ataxia, developmental delay, and tooth enamel defects (HADDTS syndrome), with predominantly de novo heterozygous missense mutations clustering in the PLDLS C-terminal domain 4. In cancer, elevated CTBP1 promotes chemoresistance and metastatic potential in esophageal squamous cell carcinoma; CRISPR-mediated CtBP1 inactivation enhances paclitaxel sensitivity 5. CTBP1 inactivation also promotes T cell persistence under chr4 stimulation 6. Additionally, the CTBP1-DT lncRNA associates with multiple cancer types and encodes a microprotein mediating cisplatin resistance 7. These findings establish CTBP1 as a critical node linking metabolism, transcriptional repression, and disease pathogenesis.