SV2B (synaptic vesicle glycoprotein 2B) is a 12-transmembrane protein localized to synaptic vesicles that plays multiple roles in neurotransmission and serves as a receptor for botulinum neurotoxins 1. As part of the SV2 family, SV2B functions in regulating vesicular calcium sensitivity, maintaining the releasable pool of vesicles, and ensuring efficient neurotransmitter release 1. The protein serves as a high-affinity receptor for botulinum neurotoxin type A (BoNT/A), where glycosylation enhances but is not essential for this interaction 2. Recent structural studies reveal that SV2B adopts a luminal-occluded conformation when bound to anticonvulsants, resembling an inhibited transporter state 3. Beyond its synaptic function, SV2B demonstrates significant disease relevance. In TFE3-rearranged renal cell carcinoma, SV2B acts as a TFE3 target gene that promotes tumor progression by interacting with HERC2 to prevent NF-κB subunit degradation, activating oncogenic NF-κB signaling 4. In glioblastoma, high SV2B expression correlates with poor prognosis and is regulated by downregulated miR-34a and miR-128 56. These findings establish SV2B as both a critical synaptic protein and a potential therapeutic target in cancer and neurological disorders.