Platelets are important mediators of haemostasis and thrombosis. Current research on antiplatelet therapy gives little attention to the role of the atypical endothelium in atherothrombosis and there is a demand for treatments that reduce thrombosis but concurrently preserve haemostasis. RhoA is a member of the Rho Family of small G proteins that act as the bridge between extracellular signals and the swift cytoskeletal restructuring of platelets leading to spreading, aggregation and thrombus formation. Vascular endothelial cells release prostacyclin (PGI2) and nitric oxide (NO) to maintain platelets in a resting state. PGI2 and NO increase intracellular levels of cAMP and cGMP causing cyclic nucleotide dependent kinase activation (PKA/G) which phosphorylate a substantial group of substrate proteins leading to functional modifications. In platelets this RhoA activity has previously been shown to be inhibited by cyclic nucleotide signalling which potentially has significant ramifications in the capacity of cyclic nucleotides to inhibit platelet activation. Through bioinformatic screening of RhoA regulatory proteins we have identified Rho GTPase activating protein 6 (RhoGAP6 – terminates RhoA signalling) and Rho guanine nucleotide exchange factor 2 (RhoGEF2 – activates RhoA) as potential new PKA/G targets. We have shown that RhoGAP6 and RhoGEF2 are expressed in platelets and have confirmed their activity towards RhoA in transfected cells using pull down assays. RhoGEF2 is phosphorylated on serine 886 by PKA/G in platelets. This phosphorylation may be linked to binding of RhoGEF2 with the 14-3-3 adaptor protein. RhoGAP6 phosphorylation sites are currently being investigated with functional studies on these sites to be conducted. The discovery of new platelet proteins RhoGAP6 and RhoGEF2 and PKA/G phosphorylation targets in platelets provides a deeper insight into the molecular mechanisms of platelet regulation which might aid in the development of new diagnostic and/or therapeutic options in thrombotic vascular disease.