GOF mutations in the RLR members IFIH1 (encoding MDA5) and DDX58 (encoding RIG-I) have been associated with several rare, inherited autoimmune diseases, including classical and atypical SMS, certain subtypes of AGS, and SLE, all characterized by elevated levels of IFN-I (Bursztejn et al., 2015; Jang et al., 2015; Rice et al., 2020; Table 1). The gene discussed is RIGI; the disease is Aicardi-Goutieres syndrome.