AbstractPresynaptic terminals maintain neurotransmitter release during repeated rounds of stimulation using local recycling of synaptic vesicles (SV). During each SV cycle, protein complex assembly and disassembly results in accumulation of inactive (unfolded) protein intermediates that may render synaptic terminals vulnerable to activity‐dependent degeneration. SV trafficking is affected in many neurodegenerative conditions including Alzheimer' and Parkinson's disease (PD) suggesting that alteration of this process might be an important aspect of disease pathogenesis. This article reviews our current understanding for a role of causative PD genes in the SV cycle and speculates on the potential role of aberrant SV trafficking in the neurodegenerative cascade of PD. © 2011 Wiley Periodicals, Inc. Develop Neurobiol 72: 134–144, 2012