G protein-coupled receptors (GPRs), also known as seven transmembrane receptors, heptahelical receptors or 7TM receptors, comprise a superfamily of proteins that play a role in many different stimulus-response pathways. G-protein coupled receptors translate extracellular signals into intracellular signals (G-protein activation) and they respond to a variety of signaling molecules, such as hormones and neurotransmitters. GPR161 (G protein-coupled receptor 161), also known as RE2, is a 529 amino acid protein that belongs to the G-protein coupled receptor family. Localized to the cell membrane, GPR161 is a multi-pass membrane protein that functions as an orphan receptor, relaying extracellular signals to the intracellular environment. Two isoforms of GPR161 exist due to alternative splicing events.