The Stimulator of Interferon Genes (STING) has a crucial role in mediating the immune response against cytosolic double-stranded DNA (dsDNA) and its activation is critically involved in various diseases. STING is synthesized, modified, and resides in the endoplasmic reticulum (ER), and its ER exit is intimately connected with its signaling. The ER, primarily known for its roles in protein folding, lipid synthesis, and calcium storage, has been identified as a pivotal platform for the regulation of a wide range of STING functions. In this review, we discuss the emerging factors that regulate STING in the ER and examine the interplay between STING signaling and ER pathways, highlighting the impacts of such regulations on immune responses and their potential implications in STING-related disorders.
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