ADAR1 mutations mapping to the Zα domain combined with alleles resulting in loss of ADAR1 or specifically its p150 isoform were shown to cause Aicardi–Goutières syndrome (AGS) and bilateral striatal necrosis (BSN) in human patients2,3 and severe MDA5–MAVS-mediated type I IFN-dependent pathology in mice6–8, indicating that the interaction of ADAR1 with Z-RNA is required to prevent activation of pathogenic IFN responses. This evidence concerns the gene IFNA1 and Aicardi-Goutières syndrome.