Munc13-4 stimulates fusion of platelet granules with the plasma membrane to release granule contents. (Top) Presecretory phase in which secretory lysosomes, platelet α-granules or dense granules, or other LRO is “docked” at the plasma membrane. Fusion requires engagement of a vSNARE (red) on the granule membrane with a tSNARE complex (green) on the plasma membrane. Munc13-4 (orange) stimulates this engagement in a calcium-dependent manner. Upon cell activation and calcium influx (bottom), the membranes fuse, releasing the contents of the granule to the extracellular space. Highlighted are examples of LRO cargoes that are known to be regulated by Munc13-4.