In all vertebrates, SV2 proteins are abundant, hydrophobic, membrane glycoproteins that are expressed as two major isoforms, SV2A and SV2B, and one minor isoform, SV2C. SV2 proteins are differentially expressed in the brain and are present on all synaptic vesicles, independent of transmitter type. SV2A is abundantly expressed in the subcortex, specifically in the synaptic vesicles of all presynaptic nerve terminals, and also in most neuroendocrine secretory granules. SV2B displays a more restricted pattern of expression in that it is only present on a small subset of synapses in the hippocampus and cortex. SV2A and SV2B are funtionally redundant and are required for maintaining normal brain function in vertebrates. SV2A and SV2B mediate synaptic transmission by regulating cytoplasmic Ca2+ levels in the nerve terminal during repetitive stimulation.