IFIH1 mutations have been implicated in autoimmune diseases, such as the gain‐of‐function mutation MDA5 G821S, which triggers the aberrant production of type I IFNs, resulting in an autoimmune response.[32] Because inactivation of AKT or USP8 destabilizes the wild‐type MDA5 protein and inhibits antiviral signaling, we hypothesize that targeting AKT or USP8 could counteract the excessive immune response induced by gain‐of‐function mutations in MDA5. Here, USP8 is linked to autoimmune disease.