CSKMT (citrate synthase lysine methyltransferase), also known as METTL12, is a mitochondrial S-adenosylmethionine-dependent protein-lysine methyltransferase that selectively trimethylates citrate synthase (CS) 12. The enzyme methylates CS on lysine residues located near the active site (Lys-395 and Lys-368), conducting trimethylation in a distributive rather than processive manner, introducing a single methyl group per binding event 2. CSKMT activity is regulated by metabolic cues: CS substrate oxaloacetate blocks methylation, while the reaction product S-adenosylhomocysteine strongly inhibits enzyme activity 2. The functional role of CS methylation remains partially unclear; while methylation does not directly affect CS catalytic activity in vitro, it may regulate substrate channeling within mitochondrial metabolons or influence protein-protein interactions in the tricarboxylic acid cycle 1. Notably, CSKMT has been identified as a candidate gene associated with anxiety disorder in rare variant analyses 3, suggesting potential neurobiological relevance beyond its established mitochondrial metabolic functions. Further investigation is needed to fully elucidate the clinical significance of CSKMT variants in psychiatric disorders.