Frontiers in immunologyJul 28, 2026

Cell cleanup of the protein-making system in inflammatory diseases

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Aug 3, 2026

Abstract

The endoplasmic reticulum is crucial for protein synthesis and is implicated in various diseases related to inflammation.

Significant structural disorganization of the endoplasmic reticulum can accelerate inflammatory responses and the progression of diseases.
Maintaining endoplasmic reticulum homeostasis may help delay inflammation.
ER-phagy, a type of selective autophagy, plays a role in integrating immune and stress signals.
ER-phagy can inhibit excessive activation of inflammatory pathways by clearing damaged components.
Research highlights the importance of ER-phagy in managing inflammation-related diseases.

Simplified

The endoplasmic reticulum (ER) is responsible for the synthesis, modification, and folding of various intracellular proteins. Under strong external stimuli, the ER often undergoes significant structural disorganization and functional abnormalities, a process that generally accelerates the onset and progression of inflammatory responses and related diseases, such as infections and sepsis, digestive system diseases, cancer, neurological disorders, circulatory diseases, and musculoskeletal diseases. Therefore, maintaining ER homeostasis is crucial for delaying the inflammatory process. As an important type of selective autophagy, ER-phagy has transcended merely "waste removal" to become a key cellular hub integrating immune and stress signals. It not only effectively curbs the excessive activation of the NF-κB pathway and the NLRP3 inflammasome by timely clearing inflammatory pathogens and ER fragments damaged by calcium store abnormalities and oxidation but also maintains immune cell homeostasis, thereby inhibiting the initiation and spread of excessive inflammatory responses. This review summarizes the key receptors, regulatory mechanisms, and the latest research on ER-phagy in various inflammation-related diseases, aiming to draw academic attention to the important value of ER-phagy in inflammatory diseases.

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Cell cleanup of the protein-making system in inflammatory diseases

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