During conditions such as rheumatoid arthritis, cold exposure or ischemia reperfusion injury, succinate is released outside of the cell.181–183 When the succinate receptor was first identified as a previously orphan G-protein coupled receptor (GPCR) SUCNR1 (formerly known as GPR91),184 this landmark study proposed that succinate in the extracellular space can act as a ligand and may have signaling properties beyond a traditional role in metabolism. The gene discussed is SUCNR1; the disease is rheumatoid arthritis.