SYT3 (synaptotagmin 3) is a calcium sensor protein that functions in Ca2+-dependent exocytosis by binding calcium and phospholipids through its C2 domain to trigger vesicle fusion 1. Beyond presynaptic neurotransmitter release, SYT3 plays critical postsynaptic roles in long-term synaptic plasticity. Specifically, SYT3 localizes to postsynaptic endocytic zones where it mediates AMPA receptor internalization in response to calcium stimulation, driving long-term depression (LTD), decay of long-term potentiation (LTP), and memory forgetting 2. SYT3 knockout mice show impaired LTP decay and complete loss of forgetting despite normal learning 2. Beyond synaptic function, SYT3 contributes to dendrite formation in melanocytes and regulates epithelial ion transport through phosphatidylserine management at ER/plasma membrane junctions 3. In metabolic contexts, hypothalamic E-Syt3 (extended synaptotagmin-3) modulates diet-induced obesity; its ablation ameliorates obesity and metabolic dysfunction while overexpression promotes weight gain 4. SYT3 also participates in lipid droplet biogenesis in adipocytes through ER-associated mechanisms 5. Dysregulation of SYT3 expression has been associated with neurological conditions, including aberrant expression patterns in Kabuki syndrome models 6.