Although nuclear cGAS accounts for 85–95% of the total, its actual contribution may be underestimated due to its tight binding with chromatin; recent studies have revealed that dysregulation of nuclear cGAS directly leads to Aicardi–Goutières syndrome, challenging the traditional understanding that “cGAS is only activated in the cytoplasm”. The gene discussed is CGAS; the disease is Aicardi-Goutières syndrome.