Biological definitions of synucleinopathies should be anchored in clinical trajectories and encompass the complex biology of the disease.

Recently, two proposals for defining Parkinson's disease and its related pathogenic processes have been published. In this viewpoint, we discuss the primary drivers behind these efforts, the future directions, and the challenges that must be addressed. While finding biomarkers is a mandatory step for better precision medicine and optimal patient stratification in therapeutic trials, we argue that a biological definition of Parkinson's disease based on a single biomarker will struggle to account for the complexity of the mechanisms involved in developing the disease. Additionally, a biological definition of asymptomatic patients should rely on a thorough understanding of patients' clinical trajectories, which is currently not the case in synucleinopathies.