α-Synuclein is an abundant neuronal protein that is highly enriched in presynaptic nerve terminals. α-synuclein regulates synaptic vesicle trafficking and subsequent neurotransmitter release. Genetics and neuropathology studies link α-synuclein to Parkinson's disease (PD) and other neurodegenerative disorders. Accumulation of misfolded oligomers and larger aggregates of α-synuclein defines multiple neurodegenerative diseases called synucleinopathies, but the mechanisms by which α-synuclein acts in neurodegeneration are unknown.