The cGAS–STING signalling pathway has emerged as a key mediator of inflammation in the settings of infection, cellular stress and tissue damage. Underlying this broad involvement of the cGAS–STING pathway is its capacity to sense and regulate the cellular response towards microbial and host-derived DNAs, which serve as ubiquitous danger-associated molecules. Insights into the structural and molecular biology of the cGAS–STING pathway have enabled the development of selective small-molecule inhibitors with the potential to target the cGAS–STING axis in a number of inflammatory diseases in humans. Here, we outline the principal elements of the cGAS–STING signalling cascade and discuss the general mechanisms underlying the association of cGAS–STING activity with various autoinflammatory, autoimmune and degenerative diseases. Finally, we outline the chemical nature of recently developed cGAS and STING antagonists and summarize their potential clinical applications.

cGAS–STING 信号通路已成为感染、细胞应激和组织损伤环境中炎症的关键介质。cGAS–STING 通路广泛参与的基础是其感知和调节细胞对微生物和宿主衍生 DNA 的反应的能力，这些 DNA 是无处不在的危险相关分子。对 cGAS-STING 通路的结构和分子生物学的深入了解使得选择性小分子抑制剂的开发成为可能，这些抑制剂有可能在人类的许多炎症性疾病中靶向 cGAS-STING 轴。在这里，我们概述了 cGAS-STING 信号级联的主要元素，并讨论了 cGAS-STING 活性与各种自身炎症、自身免疫和退行性疾病相关联的一般机制。最后，