The DNA-sensing cGAS–cGAMP–STING pathway, which drives the production of type I interferon (IFN) and other proinflammatory cytokines, must be tightly regulated to avoid chronic or autoinflammatory responses. Many studies have suggested cross-regulation between lipid metabolism and innate immune pathways, in particular the anti-inflammatory effects of liver X receptor (LXR) signalling, but the mechanisms have been unclear. Hou et al. report that LXR agonists inhibit STING signalling by promoting degradation of the second messenger 2′3′-cyclic GMP–AMP (cGAMP).