Translating Parkinson disease genetics into clinical benefit

Parkinson disease (PD) is a heterogeneous neurodegenerative disorder characterized by variable progression and treatment response. Over the past three decades, genetic discoveries have reshaped our understanding of PD biology, identifying rare monogenic forms, strong genetic risk variants and a large set of common and rare genetic variants variably contributing to PD heritability. These findings led to the identification of key pathways implicated in the neurodegenerative process, including protein misprocessing, lysosomal and mitochondrial impairment, and altered immune response. In this Review, we describe the evolution of PD genetics and discuss its current clinical impact and future role in shaping precision medicine, from diagnosis and prognosis to the development of disease-modifying therapies. Genetic information is increasingly used to support clinical decision-making, improve patient counselling and identify biologically distinct forms of PD. Importantly, genetic insights are driving therapeutic innovation, enabling targeted strategies and genetically stratified clinical trials. Despite ongoing challenges such as incomplete penetrance, variable expression of disease and missing heritability across multiple ancestries, integrating genetic knowledge into research and clinical practice is accelerating the transition towards precision medicine in PD, providing a framework for more personalized care and improved patient outcomes.