In this issue of Blood, Meng et al and Sharda et al use the Hermansky-Pudlak syndrome (HPS) as a model to show that adenosine 5′-diphosphate (ADP) released by dense granules serves as an autocrine signal to potentiate platelet release of α-granule and lysosome cargo and protein disulfide isomerase (PDI), all of which serve to stabilize thrombus formation.