Aicardi-Goutières syndrome (AGS) is a well-characterized monogenic type I interferonopathy presenting with prominent neurologic manifestations. Among extraneurologic features, renal involvement has been described in only 1 patient with an IFIH1 mutation in whom membranous nephropathy developed. The pathogenic role of augmented interferon (IFN) signaling in tissues other than the central nervous system remains to be elucidated. We report a case of collapsing glomerulopathy in a 15-year-old girl affected by AGS with RNASEH2B mutation (an alanine-to-threonine change at amino acid 177), which led to kidney failure.