CGAS and Aicardi-Goutières syndrome: Considering that IFN-I drives the overexpression of cGAS via a positive feedback loop (42), it is tempting to speculate that the Mn2+-induced activity of cGAS might underpin many type-I interferonopathies that do not involve pathogen infection (i.e. sterile inflammation), which include manganism (32), Parkinson's disease (43,44), and a wide range of autoimmune disorders such as Aicardi-Goutieres syndrome and systemic lupus erythematosus (7–10).