VAMP4 (vesicle-associated membrane protein 4) is a v-SNARE protein that plays critical roles in intracellular vesicle trafficking and membrane fusion events. VAMP4 is predominantly localized to the trans-Golgi network (TGN) and functions in retrograde trafficking from early endosomes to the TGN 1. The protein is essential for maintaining the ribbon-like structure of the Golgi apparatus, as VAMP4 depletion leads to Golgi fragmentation while preserving normal stacking 1. VAMP4 contains an N-terminal extension with a dominant TGN-targeting signal consisting of a di-leucine motif and acidic clusters 2. In pancreatic β cells, VAMP4 regulates insulin homeostasis by targeting insulin secretory granules to lysosomes through SNARE complex formation with STX7, STX8, and VTI1B, controlling insulin levels in response to glucose 3. The protein also facilitates fatty acid uptake in muscle stem cells during injury-induced regeneration by forming STX11/SNAP23/VAMP4 SNARE complexes 4. In immune cells, VAMP4 is required for cytotoxic granule exocytosis in NK cells, working alongside VAMP7 to enable cytolytic activity 5. Genetic variants in VAMP4 may modulate Parkinson's disease risk in patients with LRRK2 mutations 6.