Here, in a real-world approach study, we report our off-label experience of the use of JAK1/2 inhibition in 11 patients with AGS, with a median follow-up of 17 months (range 12 to 48 months) providing extensive clinical (AGS neurologic severity scale [8, 14]; polyhandicap severity scale [15]; dystonia rating [16–18]; caregiver assessment of activities of daily living [19]), radiological, and biological data. The gene discussed is JAK1; the disease is Aicardi-Goutieres syndrome.