Inhibition of the catalytic activity of USP30 with MTX115325 leads to robust protection of TH+ neurons in the SNpc and preservation of dopamine and its metabolites in the striatum, consistent with the protective effects resulting from KO of Usp30. Our results highlight that inhibition of the USP30 catalytic activity is promising as a potential therapeutic strategy for PD. Here, TH is linked to Parkinson disease.