?-Synuclein (?-syn) is an abundant, soluble, presynaptic protein implicated in Parkinson�s disease (PD), but its physiological functions remain unknown. In order to elucidate this function, ???-synuclein knockout (???-syn KO), mice lacking all murine synucleins were generated. Levels of the endocytic protein endophilin and the phosphorylation state of amphiphysin 2 (another endocytic protein structurally similar to endophilin) are alterated in ???-syn KO brains, suggesting that ?-syn normally functions in synaptic vesicle endocytosis (SVE) and recycling (SVR). We are testing the hypothesis that ?-syn forms a complex with endocytic proteins thereby controlling their phosphorylation and interactions. Our hope is that this work will establish whether the synucleins play a role in the endocytic limb of the synaptic vesicle exo-endocytic cycle. This research will contribute to our understanding of Parkinson�s disease (PD) and other neurodegenerative diseases related to synuclein.