Inactivating mutations in the PRKN gene encoding the ubiquitin ligase PARKIN are a leading cause of Autosomal Recessive Juvenile Parkinsonism (ARJP), a neurodegenerative disease characterized by early dysfunction and death of dopaminergic neurons in the substantia nigra pars compacta (SNc). Harnessing this mutation to create an early-onset Parkinson’s disease (PD) mouse model would provide a unique opportunity to clarify the mechanisms involved in the neurodegenerative process and lay the groundwork for the development of neuroprotective strategies. By using CRISPR/Cas9 technology, we created a knock-in mouse carrying the homozygous PrknR275W mutation, which is the missense mutation with the highest allelic frequency in PRKN patients. In PrknR275W mice, we analysed the motor phenotype as well as the anatomical and functional integrity of the nigrostriatal pathway, including striatal DA content and stimulus-evoked striatal dopamine (DA) release. We report here that PrknR275W mice show progressive motor impairment along with early DA neuron dysfunction, age-dependent loss of DA neurons in the substantia nigra, decreased DA content and release in the striatum. Together, these data show that the PrknR275W mouse recapitulates key features of ARJP. This study fills a critical need in the field by introducing a promising new PD model in which to study causative mechanisms of the disease and test therapeutic strategies.