STING: a multifaced player in cellular homeostasis

Abstract The stimulator of interferon gene (STING) is an important innate immune mediator of the cytoplasmic DNA sensing pathway. As a mediator known for its role in the immune response to infections, STING is also surprisingly at the center of a variety of non-infectious human diseases, including cancer, autoimmune diseases and neurodegenerative diseases. Recent studies have shown that STING has many signaling activities, including type I interferon (IFN-I) and other IFN-independent activities, many of which are poorly understood. STING also has the unique property of being continuous transported from the ER to the Golgi then to the lysosome. Mutations of STING or trafficking cofactors are associated with human diseases affecting multiple immune and non-immune organs. Here, we review recent advances in STING trafficking and signaling mechanisms based in part on studies of STING-associated monogenic inborn error diseases.