Protein ubiquitination modifications contribute to cardiomyocyte homeostasis and pathophysiology in diabetic cardiomyopathy (DCM). Yet the roles of deubiquitinating enzymes (DUBs) in DCM remain poorly defined. Here, we aimed to clarify the regulatory function of a DUB, valosin-containing protein interacting protein 1 (VCPIP1), in DCM and uncover the molecular mechanisms.