EHMT1 (euchromatic histone lysine methyltransferase 1) is a histone methyltransferase that catalyzes mono-, di-, and trimethylation of histone H3 lysine 9 (H3K9me1/2/3) in euchromatin, establishing an epigenetic mark for transcriptional repression through HP1 protein recruitment 1. Beyond histone modification, EHMT1 methylates non-histone proteins including p53 2 and contributes to DNA methylation through mechanisms independent of its methyltransferase activity. EHMT1 regulates cell cycle progression by silencing MYC- and E2F-responsive genes during G0/G1 transition and participates in brown adipocyte differentiation through PRDM16-mediated chr9 recruitment 1. EHMT1 haploinsufficiency causes Kleefstra syndrome 1, characterized by neurodevelopmental delay, intellectual disability, hypotonia, and seizures 3. The disorder exhibits broad phenotypic spectrum with genotype-phenotype associations dependent on which functional domains are disrupted: reader function disruption causes typical disease with characteristic DNA methylation signatures, while SET domain disruption alone produces milder phenotypes 3. EHMT1 controls the pace of human neuronal maturation by establishing an epigenetic barrier in progenitor cells that gradually releases transcriptional programs 4. EHMT1 also represses mitochondrial function genes in concert with BAZ2B, and elevated EHMT1 expression correlates with Alzheimer's disease progression 5. In cancer, EHMT1 contributes to epithelial-mesenchymal transition, cancer stemness, and drug resistance 6, with EHMT1/2 inhibition showing therapeutic potential in PARPi-resistant ovarian cancer 7.