HDAC9 (histone deacetylase 9) is a class IIa histone deacetylase that functions as a transcriptional corepressor through recruitment of HDAC1/HDAC3 complexes 1. The protein mediates histone and non-histone deacetylation to suppress gene expression across multiple physiological contexts 2. Mechanistically, HDAC9 regulates transcription by deacetylating histones and target proteins. In metabolic disease, acetate inhibits HDAC9 to increase H3K27 acetylation at the FGF21 promoter, improving glucose homeostasis 2. In intervertebral disc degeneration, HDAC9 stabilizes RUNX3 through deacetylation, protecting nucleopulposus cells from apoptosis 1. In vascular disease, HDAC9 deacetylates NLRP3 to activate the inflammasome and promote endothelial-mesenchymal transition 34. HDAC9 genetic variants associate with stroke and coronary artery disease risk in humans 53. HDAC9 overexpression drives acute lymphoblastic leukaemia with poor prognosis and sensitivity to histone deacetylase inhibitors 6. Elevated HDAC9 expression correlates with atherosclerotic plaque instability 3. HDAC9 dysfunction contributes to intervertebral disc degeneration, a major cause of low-back pain 1. Targeting HDAC9 through class IIa HDAC inhibitors shows therapeutic promise for atherosclerosis, metabolic disease, and leukaemia 326.