RhoA inside platelets. In response to vascular damage, shear stress, or other prothrombotic factors, the coordinated activation of intracellular signaling proteins by primary adhesion/activation and G protein–coupled receptors, as well as bidirectional signaling by unligated or ligand-bound α_IIbβ₃, exquisitely controls complex platelet functional responses and ultimately, prothrombotic and procoagulant activity. Pleines et al used megakaryocyte-targeted deletion in mice to identify functional roles for RhoA in platelets in vitro and in vivo.¹  Defining how receptor-associated signaling/cytoskeletal proteins are localized and up- or down-regulated over time as platelets are activated to form a thrombus will increase understanding of platelet-related defects where dysregulation can affect platelet size, shape, number and/or quality and lead to bleeding or thrombosis.