The proof-of-concept for this interconnection is best illustrated by the observation that inactivating mutations in genes maintaining DNA replication homeostasis—such as those encoding RNase H2, SAMHD1, or ADAR1—are pathognomonic of the Aicardi-Goutières syndrome (AGS) [19–23], a rare and severe neuroinflammatory disorder associated with systemic autoinflammation and elevated type I interferon expression. Here, SAMHD1 is linked to Aicardi-Goutieres syndrome.