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. The gene discussed is HCAR1; the disease is colitis.