Histone deacetylases (HDACs) are enzymes that remove acetyl groups from lysine residues on histones and non-histone proteins. There are 18 HDAC enzymes in humans, classified into four classes based on their zinc- or NAD+-dependent mechanisms. HDACs regulate chromatin structure and transcription by removing histone acetyl marks, while deacetylating non-histone proteins controls various cellular processes. HDAC inhibitors are potential anticancer agents and show promise for treating many diseases. The article provides an overview of HDACs, including their families, classes, catalytic mechanisms, structures, substrates, and regulation. It highlights the reversible nature of histone acetylation and the diverse functions of HDACs in gene expression and cellular processes. The article also discusses the complex regulation of HDAC activity through protein complexes, post-translational modifications, and other mechanisms.Histone deacetylases (HDACs) are enzymes that remove acetyl groups from lysine residues on histones and non-histone proteins. There are 18 HDAC enzymes in humans, classified into four classes based on their zinc- or NAD+-dependent mechanisms. HDACs regulate chromatin structure and transcription by removing histone acetyl marks, while deacetylating non-histone proteins controls various cellular processes. HDAC inhibitors are potential anticancer agents and show promise for treating many diseases. The article provides an overview of HDACs, including their families, classes, catalytic mechanisms, structures, substrates, and regulation. It highlights the reversible nature of histone acetylation and the diverse functions of HDACs in gene expression and cellular processes. The article also discusses the complex regulation of HDAC activity through protein complexes, post-translational modifications, and other mechanisms.