GPR26 is a G protein-coupled receptor with a a significant level of constitutive activity. Its effect is mediated by G(s)-alpha proteins that stimulate adenylate cyclase, resulting in an elevation of intracellular cAMP. It is specifically expressed in the central nervous system, where it regulates energy homeostasis via hypothalamic AMPK activation. Loss of this protein results in a range of metabolic issues such as hyperphagia, hypometabolism and early onset obesity. In immunohistochemistry, GPR26 has membranous positivity in the cerebral cortex, midbrain, hypothalamus, hippocampus, and amygdala. References: PLoS One. 2012;7(7):e40764, PMID: 22815809