The cGAS-STING Pathway: Insights into Regulatory Mechanisms, Disease Dysregulation, and Therapeutic Development

The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, a central hub of the innate immune system, is a key mediator of immune surveillance against abnormal cytoplasmic dsDNA: cGAS recognizes such dsDNA to synthesize 2'3'-cGAMP, which activates STING and downstream signaling to drive IFN-I and proinflammatory cytokine expression for the maintenance of homeostasis. This mechanism enables the pathway to exert multidimensional roles in physiology and pathology. Its activity is fine-tuned by post-translational modifications and non-coding RNAs. Given its critical role in linking innate immunity to disease progression, it has become a promising therapeutic target. This review summarizes the pathway’s regulatory mechanisms and pathological implications, detailing its roles in immune activation, disease dysregulation, and therapeutic development. It also addresses existing challenges and proposes future directions, aiming to provide new insights for precision therapy against cGAS-STING-associated diseases.