Lyu et al. identify the STING-ER-exit motif and the mechanism of its recognition by the COPII vesicle cargo-binding protein SEC24C. This study reveals how STING achieves controlled rather than constitutive ER exit and how COPII cargo recognition of STING can be modulated to control STING signaling.

Development of an ERAD-hijacking technology overcomes the challenges of current targeted protein degradation approaches to achieve degradation of transmembrane proteins.