EHMT2 is a histone methyltransferase that catalyzes mono- and dimethylation of histone H3 lysine 9 (H3K9me1 and H3K9me2), marks for transcriptional repression through recruitment of HP1 proteins. The enzyme also mediates H3K56 monomethylation during DNA replication and weakly methylates H3K27, while functioning in DNA methylation through mechanisms independent of its methyltransferase activity. Beyond histones, EHMT2 dimethylates non-histone proteins including p53, DNMT1, and HDAC1. Clinically, EHMT2 has emerged as a therapeutic target across multiple disease contexts. In microsatellite-stable colorectal cancer, EHMT2 inhibition remodels the immunosuppressive microenvironment by upregulating galectin-7, converting tumors to T-cell-inflamed states and enhancing anti-PD1 immunotherapy efficacy 1. EHMT2 inhibition also shows promise in mantle cell lymphoma, where the selective inhibitor BIX01294 suppressed cell growth and induced apoptosis 2. In Prader-Willi syndrome, a recently developed orally bioavailable inhibitor MS152 reactivated maternally silenced PWS genes in patient-derived cells and mouse models, ameliorating perinatal lethality and growth deficits 3. EHMT2 is also implicated in regulating human neuronal maturation timing, with transient inhibition enabling precocious neuronal maturation 4, and has been identified as a prognostic biomarker in Wilms tumor 5. Additionally, EHMT2 represents a drug target candidate for hypertension based on genetic evidence 6.