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. GPR125 (G protein-coupled receptor 125), also known as PGR21 or TEM5L, is a 1,321 amino acid multi-pass membrane protein belonging to the G-protein coupled receptor 2 family and the LN-TM7 subfamily. Considered a novel orphan adhesion-type G-protein-coupled receptor, GPR125 has five leucine rich repeats (LRR), an immunoglobulin (Ig) domain and a GPS domain. GPR125 may play a functional role in choroidal and hippocampal response to brain injury. It is also suggested that GPR125 may be a marker for spermatogonial stem cells. Four isoforms of GPR125 exists due to alternative splicing events.