Parkinson’s disease (PD) is the second most common neurodegenerative disorder for which there is no disease-modifying therapy. Pathologically, the neuronal loss correlates with abnormal accumulation, aggregation and toxic gain of function of the small pre-synaptic protein alpha-Synuclein (aSyn). Whether neurons degrade aggregated aSyn or, only its soluble monomers, remains elusive. This thesis combines hypothesis-driven and unbiased genetic screens to identify pathways that specifically regu...