Project Summary G protein-coupled seven transmembrane receptors (GPCRs) are the most common target of pharmaceutical drug development, and uncovering the function of novel GPCRs receptors in the kidneys represents a wealth of untapped therapeutic potential. Current investigations into the novel roles of sensory receptors in the kidney have enriched our understanding of renal function; for example, our lab recently identified important physiological roles for two different novel renal GPCRs (Olfr78 regulates renin secretion, whereas Olfr1393 modulates renal glucose handling). These, and numerous other studies, have demonstrated the importance of investigating previously understudied or overlooked receptors in order to uncover novel interventions for kidney disease. We recently undertook a screen for novel GPCRs in the kidney to identify promising yet overlooked renal GPCRs. This screen revealed that the understudied GPCR, Gpr116, is highly expressed in the kidney. Published RNASeq data from other labs suggests Gpr116 is found preferentially in the collecting ducts, a site of considerable Na+ and water absorption. In this proposal, we will determine its expression profile within the kidney (Aim 1) , characterize the downstream effects of Gpr116-mediated Gq- signalingon renal transport processes (Aim 2), and investigate its physiologic significance (Aim 3). In sum, we aim to determine the physiological role of Gpr116 in the kidney, with the hope of eventually exploring the therapeutic potential of Gpr116 in the treatment of renal disease. The results of these studies will provide important insight regarding the role of an understudied and overlooked receptor on kidney physiology. Moreover, successful completion of the proposed research will not only identify the biologic and clinical significance of Gpr116, but will additionally demonstrate the therapeutic potential of investigating novel and understudied GPCRs in the kidney.