Proteins contain numerous nucleophilic sites, including the cysteine thiol, the lysine e-amine, and the N-terminus . These reactive sites enable post-translational modifications that play central roles in cellular signaling and function, but protein nucleophiles are also subject to modification by environmental and metabolic electrophiles . This damage can deprive the cell of protein function , interfere with binding interactions , or promote protein misfolding and toxic aggregation . Despite the clear threat that electrophilic exposure agents present to the cellular proteome and protein homeostasis, protein conjugation by environmental toxicants is not nearly as well investigated as nucleic acid conjugation. This stems in part from the larger dynamic range for nucleophilicity in proteins as compared to nucleic acids . Nucleic acid reactivities vary far less than protein reactivities, and the mutagenic potential of nucleic acid adducts can be readily determined through well-established mutagenicity assays such as the Ames test. Assays that identify the protein targets of electrophiles and other reactive exposure agents are necessary to identify their molecular mechanisms of toxicity.