The Parkinson's Progression Marker Initiative (PPMI), sponsored by The Michael J. Fox Foundation for Parkinson's Research, is designed to develop disease biomarkers to accelerate Parkinson's disease (PD) therapeutics. During the past 15 years PPMI has acquired comprehensive clinical, imaging, biomarker and genetic data on thousands of participants that has guided clinical therapeutic studies for PD and related synucleinopathies. The study has established standardized strategies for acquisition and analysis of data and set a standard for data sharing and open-source publication. PPMI has by design consistently evolved to incorporate new knowledge and science. A key example is that PPMI data has enabled the transition from clinical to biologic definition of synucleinopathy. The study continues to expand our understanding of disease biology particularly in precise PD subsets in both in-clinic and a rapidly expanding remote participant cohort, using myPPMI, an online portal. This special issue reviews PPMI's continuing contribution to early detection, understanding disease biologic and staging, and innovative therapeutic strategies in PD and related synucleinopathies. ANN NEUROL 2026.
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