Excessive PKR activity can be detrimental, as is observed in Aicardi-Goutières syndrome patients where mutations in the adenosine deaminase 1 (ADAR1) lead to increased levels of endogenous dsRNA, thereby triggering PKR activation and uncontrolled IFN production (Chung et al., 2018). Here, EIF2AK2 is linked to Aicardi-Goutières syndrome.