A study now links platelet generation and cholesterol metabolism, providing new understanding of the mechanisms involved in thrombocytosis and atherogenesis. The authors show that the cholesterol transporter ABCG4 is highly expressed in bone marrow megakaryocyte progenitors, and in its absence, these cells have defective cholesterol efflux and increased proliferation, leading to increased megakaryocyte production, thrombocytosis and accelerated atherogenesis in atherosclerosis-prone mice (pages 586–594).