STING1 and infection: In contrast, infection-independent STING activation occurs without external pathogens and is driven by intrinsic abnormalities such as nucleic acid clearance defects (e.g., TREX1 [121,122] or DNase deficiencies [123]), gain-of-function STING mutations (e.g., SAVI [68,97]), ER stress [124], or dysregulated trafficking.