IRF3 and glycogen storage disease VI: RNF55 (c-Cbl) directly interacts with the nuclear IRF3 for promoting K48-linked poly-ubiquitination and proteasomal degradation of IRF3, thereby downregulating TLR- and RLR- mediated induction of IFN-I.274 Their study, combined with Cao’s findings, revealed the dual inhibitory function of RNF55 in RLR-mediated IFN-I signaling for the termination of excessive immune responses,211,274 indicating that the RNF55 is one of the promising new therapeutic targets for controlling excessive immune responses-related diseases.