Ceramides are potent influencers of cell fate and function; however, their direct molecular target(s) and mechanism of action are poorly understood. In this study, we treated primary proximal tubule epithelial cells with C2-ceramide (50uM) or its precursor C2-dihydroceramide (50uM) and used proteome integral solubility alteration (PISA) to identify potential ceramide-specific protein effectors.