EEF2KMT (eukaryotic elongation factor 2 lysine methyltransferase), also known as FAM86A, is a class I lysine methyltransferase that catalyzes trimethylation of eukaryotic elongation factor 2 (EEF2) at lysine-525 1. This modification is evolutionarily conserved, with functional orthologues identified in yeast 1. The enzyme contains an N-terminal FAM86 domain of previously unknown function that mediates substrate specificity and EEF2 recognition, alongside a C-terminal methyltransferase domain 2. The FAM86 domain represents a noncatalytic structural element essential for protein lysine methylation, providing substrate-specific interactions distinct from the conserved S-adenosyl methionine cofactor binding domain 2. Functionally, EEF2-Lys525 methylation is important for translation fidelity; yeast deficient in the EEF2KMT orthologue show increased frameshifting during protein translation and heightened sensitivity to translation inhibitors 1. Clinically, EEF2KMT is emerging as a cancer-relevant gene, with hundreds of human cancer cell lines showing high dependence on its expression 2. Notably, a truncating variant (p.K116*) in EEF2KMT was identified as a high-confidence stop-gain mutation segregating in familial Hodgkin lymphoma pedigrees, suggesting potential involvement in lymphomagenesis predisposition 3.