Updated project metadata. In this study we use a combination of mass spectrometry-based proteomics and biophysical studies to characterize the interaction of adaptors with VCP. Our results reveal that most VCP–adaptor interactions are characterized by exceptionally rapid dynamics that in some cases are modulated by the VCP inhibitor NMS873. These findings have significant implications for both the regulation of VCP function and the impact of VCP inhibition on different VCP–adaptor complexes.