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Schematic cartoon of the fusion of vesicles containing neurotransmitter with the outer membrane of the cell (left) at synapses and of their reformation by endocytosis (right). Vesicle reformation requires the assembly at the outer cell membrane of a complex of proteins that deform it and select components that need to be incorporated into the nascent bud. The assembly of these proteins to form a coat at the outer cell membrane requires the presence of the phospholipid, PI(4,5)P2, in this membrane. Conversely, shedding of coat proteins after endocytosis requires loss of the two phosphates from PI(4,5)P2, a process mediated by synaptojanin 1 via its 4- and 5-phosphatase domains. Synapses of mice harboring a Parkinson’s disease mutation in the 4-phosphatase domain of synaptojanin 1 reveal an accumulation of vesicles that fail to uncoat and neurological defects reminiscent of Parkinson’s disease.