Genome-wide association (GWA) studies have shown that supposedly activating IFIH1 variants – analogous to fully penetrant gain-of-function mutations underlying the dominant Mendelian diseases AGS and SMS – are implicated in the pathogenesis of autoimmune disorders such as type 1 diabetes (Nejentsev et al., 2009) and SLE (Molineros et al., 2013). Here, IFIH1 is linked to Aicardi-Goutieres syndrome.