EHMT1 encodes euchromatic histone lysine methyltransferase 1, a key epigenetic regulator that catalyzes mono-, di-, and trimethylation of histone H3 lysine 9 (H3K9me1/2/3), establishing transcriptional repression through recruitment of HP1 proteins. The enzyme also weakly methylates H3K27 and dimethylates non-histone proteins including p53. EHMT1 participates in cell cycle regulation by silencing MYC- and E2F-responsive genes during G0/G1 transition, and coordinates with PRDM16 to suppress white adipose gene expression during brown and beige adipocyte differentiation. Additionally, EHMT1 represses mitochondrial function-related genes in collaboration with BAZ2B. During cortical neurogenesis, EHMT1 contributes to an epigenetic barrier that delays human neuronal maturation by maintaining developmental programmes in a poised state 1. Biallelic EHMT1 haploinsufficiency causes Kleefstra syndrome (KLEFS1), characterized by intellectual disability, developmental delay, hypotonia, seizures, and distinctive facial features 2. Variant-specific effects shape phenotypic severity: disruption of the ankyrin repeat "reader" domain produces typical KLEFS1 manifestations with characteristic DNA methylation signatures, while SET domain methyltransferase defects or N-terminal truncations result in milder presentations 2. EHMT1 overexpression promotes cancer progression through enhanced H3K9me3 deposition, particularly in glioblastoma where it correlates with poor prognosis 3, and aberrant expression facilitates epithelial-mesenchymal transition and therapy resistance across multiple cancer types 4. In aging, elevated EHMT1 expression in frontal cortex correlates with Alzheimer's disease progression and reduced mitochondrial function 5.