STING1 is a central hub in intracellular DNA sensing that initiates potent innate immune responses. Upon activation by cyclic GMP-AMP (cGAMP) produced by cGAS, STING functions as both a signaling adapter and proton channel 1. STING undergoes palmitoylation-dependent assembly into multimeric complexes at the Golgi apparatus, recruiting downstream factors to activate interferon and inflammatory cytokine production 2. Beyond antimicrobial defense, STING regulates autophagy, inflammasome activation, and cell metabolism 3. Notably, STING drives chr5 low-grade inflammation during aging; blocking STING suppresses senescent cell phenotypes and attenuates age-related neurodegeneration and cognitive decline in mice by reducing aberrant cGAS activation in microglia responding to cytosolic DNA from dysfunctional mitochondria 4. In cancer, STING signaling paradoxically promotes both anti-tumor immunity and pro-tumor immunosuppression through induction of PD-L1 in tumor monocytes 5. Viral oncoproteins including HPV E7 and adenovirus E1A antagonize STING-mediated antiviral responses by blocking cytosolic DNA sensing 6. Dysregulation of safeguard mechanisms controlling STING activation by self-DNA causes autoinflammatory diseases 7. These findings position STING as a therapeutic target for aging-related neurodegeneration, autoinflammation, and cancer immunotherapy.