Synaptojanin 1 (SJ1) is a major presynaptic phosphatase that couples synaptic vesicle endocytosis to the dephosphorylation of PI(4,5)P2, a reaction needed for the shedding of endocytic factors from their membranes. While the role of SJ1’s 5-phosphatase module in this process is well recognized, the contribution of its Sac phosphatase domain, whose preferred substrate is PI4P, remains unclear. Recently a homozygous mutation in its Sac domain was identified in early-onset parkinsonism patients. We show that mice carrying this mutation developed neurological manifestations similar to those of human patients. Synapses of these mice displayed endocytic defects and a striking accumulation of clathrin-coated intermediates, strongly implicating Sac domain’s activity in endocytic protein dynamics. Mutant brains had elevated auxilin (PARK19) and parkin (PARK2) levels. Moreover, dystrophic axonal terminal changes were selectively observed in dopaminergic axons in the dorsal striatum. These results strengthen evidence for a link between synaptic endocytic dysfunction and Parkinson’s disease. •Parkinsonism patient mutation in SJ1 produces motor dysfunction in mice•A role of the Sac domain of SJ1 (PARK20) in clathrin coat dynamics at synapses•Selective disruptive impact on a subset of nigrostriatal axons of the SJ1 mutation•Knockin mice for the SJ1 mutation have abnormal levels of PARK2 and PARK19 Cao et al. demonstrate widespread synaptic accumulation of clathrin-coated endocytic intermediates and an additional selective dystrophy of a subset of nigrostriatal dopaminergic axon terminals in knockin mice carrying the synaptojanin 1 (PARK20) mutation responsible for early-onset parkinsonism.