Dysregulation of USP30 is implicated in a range of rare genetic mitochondrial diseases, and neurodegenerative diseases including Parkinson's disease.12 Accordingly, there is significant interest in developing USP30 inhibitors for the clinic, and Mission Therapeutics initiated the first clinical trials of a USP30 inhibitor in 2022 for muscular, cardiac and kidney pathologies,34 reporting encouraging Phase I safety data. Here, USP30 is linked to neurodegenerative disease.