Human GPR99 also known as GPR80 is a G protein-coupled receptor with 337 amino acids. The mRNA of GPR99 was shown to be expressed predominantly in the kidney. Phylogenetic analysis groups GPR99 into the P2Y subfamily of GPCRs. However, deorphanization studies show that it is a close a relative of GPR91 and have proposed the citric acid cycle intermediate alpha-Ketoglutarate as a ligand for GPR99 receptor. The receptor couples to Gq upon ligand binding, promoting intracellular calcium increase and inositol phosphate accumulation.