GPR21 is a member of the G-protein-coupled receptor 1 family. G-protein coupled receptors are membrane proteins which activate signaling cascades as a response to extracellular stress. The encoded protein activates a Gq signal transduction pathway which mobilizes calcium. GPR21 exerts effects on the insulin signaling pathway (for example, it attenuates signaling when overexpressed), and inhibiting GPR21 is of interest in treating diabetes. In immunohistochemistry, GPR21 has membranous positivity that is putatively most prominent in the central nervous system, although it has low to variable expression in most other tissues. It is found in the thalamus, on nonpigmented neurons in the substantia nigra, on large pyramidal neurons in the caudate, putamen and amygdala, on granule neurons in the hippocampus, in the posterior nucleus of the hypothalamus, and on populations of cells in the anterior pituitary (as well as in Herring bodies in the posterior pituitary). In peripheral tissues, it is found on hepatocytes, spermatocytic precursors, neuroendocrine cells in the small intestine, neutrophils, populations of basally-oriented cells in breast epithelium, sweat lobules in the skin, and on a few other cell types in various tissues throughout the body. References: Sci Rep. 2016; 6: 27002, PMID: 27243589