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We report the association of early\u2010onset parkinsonism with the <jats:italic>PPP2R5D<\/jats:italic> p.E200K mutation. Clinical characterization and exome sequencing were performed on three patients, with postmortem neuropathologic examination for one patient. All patients had mild developmental delay and developed levodopa\u2010responsive parkinsonism between the ages of 25 and 40\u2009years. The <jats:italic>PPP2R5D<\/jats:italic> c.598G&gt;A (p.E200K) mutation was identified in all patients<jats:italic>.<\/jats:italic> Neuropathologic examination demonstrated uneven, focally severe neuronal loss and gliosis in the substantia nigra pars compacta, without Lewy bodies. Our findings suggest the <jats:italic>PPP2R5D<\/jats:italic> p.E200K mutation to be a possible new cause of early\u2010onset parkinsonism. 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