Alternatively, a variety of proteome-wide methods assay changes in protein conformation or stability in response to exposure. These techniques, which include Stability of Proteins from Rates of Oxidation (SPROX), Fast Photochemical Oxidation of Proteins (FPOP), limited proteolysis (LiP), and Covalent Protein Painting (CPP), provide residue-level interrogation of protein solvent accessibility . Each has been successful at revealing ligand targets, and SPROX in particular has successfully identified targets of exogenous toxicants . Still, these techniques require profiling of the entire proteome, which inherently challenges their depth. We previously developed an affinity purification mass spectrometry (AP-MS) approach to profile the misfolded proteome using human the Hsp40 DNAJB8 . This assay combines affinity purification of overexpressed Flag DNAJB8 H31Q with quantitative proteomics to identify hundreds of co-isolating cellular proteins with high reproducibility and statistical confidence . The H31Q mutation blocks the release of misfolded protein clients from DNAJB8, making it a thermodynamic sink for its clients. This binding is highly detergent-resistant, allowing immunoprecipitates to be stringently washed.