Rett syndrome is a severe neurodevelopmental disorder in girls, underpinned by mutations in the X-linked gene MECP2. In their recent work (Frasca et al, 2024), Frasca and colleagues identified a novel pathway involving interferon-gamma (IFNγ) that could pave the way to potential therapies. Here, MECP2 is linked to atypical Rett syndrome.