The Histone Methyltransferase (HMT) family, which includes SET and non-SET domain proteins, primarily functions within the cell nucleus to regulate gene expression and chromatin states. By adding methyl modifications to lysine or arginine residues of histones, HMTs influence chromatin density, thereby modulating gene activation or silencing. These enzymes participate in various biological processes, including DNA damage repair, cell cycle control, and development. HMTs exhibit specific expression patterns in different cell types and tissues, and their dysregulated activity or gene mutations are associated with various diseases, including cancer, cardiovascular diseases, and neurodegenerative diseases. The intricate regulatory networks of HMTs reflect their central role in cellular function.