The ER–Golgi intermediate compartment: a central hub integrating membrane trafficking and stress responses

Abstract

The endoplasmic reticulum–Golgi intermediate compartment (ERGIC) is a dynamic membrane system at the ER–Golgi interface, traditionally viewed as a transient station for COPII- and COPI-dependent trafficking. Emerging evidence redefines the ERGIC as a stress-responsive regulatory hub that integrates membrane trafficking with cellular adaptation. In addition to coordinating bidirectional transport and cargo sorting, the ERGIC actively participates in protein quality control during ER stress and remodels trafficking flux under perturbations. It serves as a platform linking secretory pathways to stress signaling, contributing to autophagosome biogenesis, facilitating unconventional protein secretion under stress conditions, and modulating innate immune responses, including STING activation. The ERGIC is also co-opted by pathogens such as coronaviruses, underscoring its role at the interface of membrane remodeling and host defense. These functions position the ERGIC as a central integrator of trafficking dynamics and stress responses, whose structural plasticity enables rapid adaptation to physiological and pathological challenges. This review provides a comprehensive discussion of the ERGIC, which emerges as a central hub integrating membrane trafficking and the cellular response to stress. It participates in protein quality control, autophagosome biogenesis, unconventional secretion and STING-dependent innate immune responses.