The present invention relates to low-density lipoprotein receptor related protein 6 (LRP6). More specifically, the present invention relates to targeting of LRP6 to modulate Gαs activity. In one embodiment, a method of screening for antagonists of IRP6-Gαs interaction comprises the steps of (a) contacting an agent that binds LRP6 with a cell and (b) measuring the level of cAMP production in the cell in response to one or more GPCR ligands, wherein an agent that decreases cAMP production as compared to cAMP production in the cell not contacted with the agent identifies the agent as an antagonist of LRP6-Gαs interaction.
