SNARE proteins are required for membrane fusion in various intracellular compartments of all eukaryotic cells. At synapses v-SNARE Synaptobrevin-2/VAMP-2 forms tight fusogenic assembly termed core complex with t-SNAREs Syntaxin 1 and SNAP-25. The function of each of the three SNAREs is essential for synaptic vesicle exocytosis and normal synaptic transmission. Another v-SNARE protein, VAMP4 is also present on synaptic vesicles and can form core complex with Syntaxin 1 and SNAP-25 in vitro, however synaptic function of VAMP4 is not known. This presentation will focus on our recent work on the trafficking and putative role of VAMP-4 in central synapses. We found that VAMP-4 is widely expressed in neurons and internalized at the synapses upon stimulation. Also, despite VAMP-4 can form SNARE- complexes in vitro, it failed to rescue synaptic vesicle release in VAMP-2 knock-out neurons. In order to understand the fundamental differences between VAMP-2 and VAMP-4 we manipulated their structure and monitored their trafficking and ability to support neurotransmitter release. To date, our results suggest a role for VAMP-4 in regulation of endocytosis rather than exocytosis providing an example of functional selectivity among vesicular SNARE proteins.