The objective of this project was to determine the interaction interface(s) between acid beta-glucosidase (GCase) and its activator protein saposin C (SapC). Chemical crosslinking was used to confirm the formation of discrete heterodimers between the two proteins, using lysine-reactive crosslinkers BS3 and DTSSP and both non-activating and activating buffer systems. High-resolution mass spectrometry was then used to determine the sites of crosslinking, which informed the modes of protein-protein interactions. We identified two binding surfaces between GCase and saposin C using this workflow.