Two studies published in this issue of JEM, by Lepelley et al.(https://doi. org/10.1084/jem. 20200600) and Deng et al.(https://doi. org/10.1084/jem. 20201045), and two additional manuscripts by Mukai et al.(https://doi. org/10.1101/2020.05. 20.107664 Preprint v1) and Steiner et al.(https://doi. org/10.1101/2020.07. 09.194399 Preprint v1) demonstrate that COPA syndrome–associated high interferon titers are linked to mutations in COPA preventing STING’s retrieval from the Golgi back to the ER and thereby causing chronic immune activation.