G protein-coupled receptors (GPRs) are a protein family of transmembrane receptors that transmit an extracellular signal (ligand binding) into an intracellular signal (G protein activation). GPR signaling is an evolutionarily ancient mechanism used by all eukaryotes to sense environmental stimuli and mediate cell-cell communication. All of the receptors have seven membrane-spanning domains and the extracellular parts of the receptor can be glycosylated. These extracellular loops also contain two highly conserved cysteine residues which create disulfide bonds to stabilize the receptor structure. GPR105, also designated P2Y14, is widely expressed throughout many brain regions where it localizes to glial cells, and specifically co-localizes with astrocytes. GPR105 is upregulated when a tissue is immunologically challenged with lipopolysaccharide, leading to the theory that GPR105 may play an important role in modulating peripheral and neuroimmune function.