Synapsins are synaptic vesicle-associated phosphoproteins that regulate synaptic vesicle exocytosis and may be involved in synaptogenesis. Evidence suggests that Synapsin I, Synapsin II and Synapsin IIIa are ATP-binding proteins that are regulated by Ca2+ and calmodulin binding. Ca2+ has been shown to stimulate ATP binding to Synapsin I, to have no effect on Synapsin II and to inhibit Synapsin III. Synapsin I and Synapsin II both undergo alternative splicing to produce two forms of each protein, Synapsin la and lb and Synapsin IIa and IIb, respectively. Synapsin III gives rise to at least three isoforms: Synapsin IIIa, IIIb and IIIc. Synapsin III plays unique roles both in early axon outgrowth and in the regulation of synaptic vesicle trafficking. In cultured mouse hippocampal neurons, synapsin III is expressed early during development, with levels peaking seven days after plating and declining thereafter. Synapsin III is highly concentrated in growth cones.