More than one-sixth of the human proteome contains methylation on a lysine residue, yet little is known about the function of these lysine methylation events. In general, it is appreciated that post-translational modifications (PTMs) are molecular signals, strung together to create signaling cascades that regulate nearly every cellular process. Lysine methylation was discovered around the same time as phosphorylation, yet our understanding of lysine methylation signaling lags decades behind. The Cornett lab uses in vitro and cellular biochemistry, chemical biology, and proteomic approaches to map lysine methylation signaling networks and study the function of lysine methylation on non-histone proteins.