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Methylation of p53 protein by KMT7/SET7 is the first reported KMT-mediated methylation event on a non-histone protein 18 Since that discovery, several KMTs, as well as KDM1A, have been identified as p53 regulators that methylate or demethylate p53 protein, making p53 the most extensively studied non-histone protein undergoing lysine methylation 4 , 13 , sixteen , 18 , 162 Here we use p53 as a model to debate the functions of lysine methylation of non-histone proteins.