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The synaptic vesicle glycoprotein 2 (SV2) family comprises **SV2A**, **SV2B**, and **SV2C**—closely related 12-transmembrane domain glycoproteins present on synaptic vesicles of neurons and neuroendocrine cells[1][2][7]. These proteins are not classical receptors or enzymes, but play essential roles in synaptic vesicle trafficking, exocytosis, and transmitter release by modulating a variety of presynaptic processes, including vesicular calcium sensitivity and the maintenance of readily releasable vesicle pools. **SV2A** is the main isoform in the brain and is the direct target of antiepileptic drugs such as levetiracetam and brivaracetam. SV2 proteins are also exploited by botulinum neurotoxins to access nerve terminals, and growing evidence suggests involvement in neurodegenerative disorders (notably for SV2B and SV2C). Diagnostic imaging of SV2A using PET tracers is increasingly important as a proxy for synaptic density in clinical research[2][7]. Despite intensive study, the precise mechanistic functions of these proteins remain incompletely defined, and their roles may extend beyond neurotransmitter regulation to include vesicle metabolic homeostasis, such as galactose transport (at least for SV2A)[6].
Binding of antiepileptic drugs to SV2A modulates synaptic transmission and reduces neuronal hyperexcitability Botulinum toxins bind to SV2 proteins to enter neurons and inhibit neurotransmitter release
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