This class of G protein-coupled receptors is characterized by their lack of a known ligand. Through the use of pharmacological inhibitors and knock-out mice, however, many have been linked to specific functions and associated diseases. Some examples include GPRC5A, which is a tumor suppressor, possibly exerting its effects via inhibition of STAT3 signaling. GPR3 has been linked to beta-amyloid production and may have a role in Alzheimer's disease progression. GPR50 antagonizes melatonin receptor 1 and plays in important role in adaptive thermogenesis and torpor. GPR22 is expressed in the brain and heart and plays a cardio protective role in response to hemodynamic stress. GPR114 likely has an immune function, as it is expressed in lymphocytes and granulocytes. GPR15 has been well established as an HIV co-receptor, but little is known of its endogenous function.