Platelet homeostasis, i.e. a stable platelet count in the circulation, is dependent on a tight regulation of both platelet production and clearance. Dr. Robert Lee, in collaboration with members of the Bergmeier lab, the Flick lab, and international collaborators, recently published their studies on the effect of uninhibited signaling by the small GTPase Rap1 on platelet homeostasis. Their findings, published in the Journal of Clinical Investigation Insight, describe a novel, integrin-based mechanism of platelet clearance that could be critical for our understanding of select inherited and acquired thrombocytopenias.