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Review
. 2025 May;68(5):1309-1323.
doi: 10.1007/s11427-024-2808-3. Epub 2025 Jan 14.

cGAS-STING: mechanisms and therapeutic opportunities

Mengyuan Zhang  1   2 , Changxin Wu  3 , Defen Lu  4 , Xing Wang  5   6 , Guijun Shang  7   8
Affiliations
Review

cGAS-STING: mechanisms and therapeutic opportunities

Mengyuan Zhang et al. Sci China Life Sci. 2025 May.

Abstract

The cGAS-STING pathway plays a crucial role in the innate immune system by detecting mislocalized double-stranded DNA (dsDNA) in the cytoplasm and triggering downstream signal transduction. Understanding the mechanisms by which cGAS and STING operate is vital for gaining insights into the biology of this pathway. This review provides a detailed examination of the structural features of cGAS and STING proteins, with a particular emphasis on their activation and inhibition mechanisms. We also discuss the novel discovery of STING functioning as an ion channel. Furthermore, we offer an overview of key agonists and antagonists of cGAS and STING, shedding light on their mechanisms of action. Deciphering the molecular intricacies of the cGAS-STING pathway holds significant promise for the development of targeted therapies aimed at maintaining immune homeostasis within both innate and adaptive immunity.

Keywords: STING; activation; autoinhibition; cGAMP; cGAS; proton channel.

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Conflict of interest statement

Compliance and ethics. The authors declare that they have no conflict of Interest.

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