CDYL (chr6 Y like) is a transcriptional corepressor that functions through multiple mechanisms to regulate gene expression and cellular processes. CDYL acts as a bridge between the transcriptional repressor REST and histone methyltransferases like G9a, facilitating chr6 modifications for gene silencing 1. Notably, CDYL functions as a crotonyl-coenzyme A hydratase that negatively regulates histone crotonylation, affecting diverse cellular pathways including DNA repair through regulation of RPA1 crotonylation 2. The protein plays critical roles in development, particularly in maintaining forebrain identity in human cortical organoids by inhibiting neuronatin expression and controlling neural stem cell fate determination 3. CDYL demonstrates significant disease relevance across multiple pathologies. In cancer, CDYL functions as a tumor suppressor, with knockdown inducing oncogenic transformation through derepression of proto-oncogenes like TrkC 1. However, circular RNAs derived from CDYL can promote cancer progression and immune evasion in hepatocellular carcinoma 4. In kidney disease, CDYL inhibition ameliorates acute kidney injury by regulating tubular pyroptosis 5. Clinically, CDYL represents a potential therapeutic target, with selective small-molecule inhibitors showing promise in treating acute kidney injury without significant side effects 5.