In mouse macrophages and human monocytes, GPR81 activation suppresses Toll-like receptor pathways, preventing NLRP3 (NACHT, LRR and PYD domains-containing protein 3) inflammasome activation and cell death.11 This mechanism appears protective, with receptor activation reducing tissue injury in models of hepatitis, pancreatitis,11 and colitis.12 GPR81 inhibition/knockdown has also been shown to be protective, enhancing neuron survival in cerebral ischemia13 and slowing cancer growth,14,15 partly due to effects on the vasculature. This evidence concerns the gene HCAR1 and cancer.