Neurons in our brain are organized in circuits and communicate using synaptic vesicles that release neurotransmitters upon fusion with the membrane. Synapses are often far away from their cell bodies, where the DNA resides and where most proteins are produced. Given that synapses are metabolically very active and are packed with proteins and lipids needed for continued neurotransmission, synapses must harbor mechanisms to maintain protein and lipid function. Deregulation of these mechanisms may cause disease, a feat underscored by the accumulation of aggregated or unfolded proteins in many neurodegenerative diseases. We study mechanisms of protein homeostasis and neurotransmission in healthy and diseased neurons with an emphasis on Parkinson’s disease, the second most commone neurodegenerative disease. In our studies we are using human neurons derived from embryonic stem cells, but also fruit fly genetics allowing us to conduct large scale genetic screens. We are combining these models with a variety of functional in vivo assays including electrophysiology, live imaging and advanced electron microscopy including electron tomography and block face scanning EM.