In this issue of Molecular Pharmacology, Andreeva et al. (p. 975) report a novel functional link between the heterotrimeric G protein G alpha12 and endothelial nitric-oxide synthase (eNOS). Based on studies characterizing the interaction of G alpha12 and the molecular chaperone Hsp90 and the interaction of eNOS and Hsp90, the group proposed an interaction between G alpha12 and eNOS and sought to determine the regulatory mechanisms, including the inferred dependence on Hsp90. Their experiments using an overexpression model lead to the observation that the cotransfection of G alpha12 and eNOS expression vectors increased overall eNOS expression. Additional studies in the overexpression model and in human umbilical vein endothelial cells (HUVEC) provide evidence for a mechanism that involves G alpha12-dependent stabilization of eNOS protein and possibly mRNA. These data present yet another paradigm by which heterotrimeric G proteins, through stabilization of target proteins, can regulate the activity of downstream signaling pathways.