The GPCR receptors GPR40, GPR41, GPR42, and GPR43 were identified as orphans during random sequencing of their common chromosomal location. Lower levels of GPR41 were detected in the spleen and peripheral blood mononuclear cells, as well as the pancreas, lung, and numerous other tissues. However, GPR41 showed positive staining of endothelial cells, particularly in white adipose tissue and also lymphocytes of the tonsil and a subset of lymphocytes in the trachialbronchial lymph node. Notably, in contrast to GPR40 and GPR43, no expression was detected in monocytes. Knockout mouse studies have implicated GPR41 in diabetes, colitis, hypertension and asthma. Furthermore, GPR41 activation by either acetate or synthetic agonists, led to reduced cytokine expression in human monocytes.