Taken together, we identified the parkin V380L variant as a novel genetic modifier with a deciphered, mitophagy-related contribution to the molecular pathogenesis in MJD, which may allow for a more precise prognostic evaluation of patients suffering from this yet incurable disorder, and reveal a potential target for the development of a treatment strategy. This evidence concerns the gene PRKN and Spinocerebellar ataxia type 3.