Background: The endoplasmic reticulum (ER) is a critical organelle responsible for the folding, modification, and transport of proteins. Perturbations to this process lead to an accumulation of misfolded proteins, a condition known as ER stress. The unfolded protein response (UPR) is a complex signaling network that is activated to restore protein homeostasis. While the UPR is an essential adaptive mechanism for cellular survival, its chronic activation is implicated in the progression of various pathologies.

Main Body: This review synthesizes current knowledge on the ER stress response, detailing its molecular mechanisms and its dual role in maintaining cellular health and contributing to disease states. Initially, the UPR orchestrates a series of adaptive measures, including the downregulation of global protein synthesis and the upregulation of chaperone proteins to alleviate the protein folding burden. However, sustained or unresolved ER stress triggers pro-apoptotic pathways, leading to cellular dysfunction and death. This chronic state is a key factor in the pathogenesis of a range of diseases, including neurodegenerative disorders, metabolic syndromes, and cancer. The interplay between ER stress, inflammation, and cellular homeostasis is also explored, highlighting the intricate regulatory networks that govern cellular fate.

Conclusion: A comprehensive understanding of the ER stress response is crucial for developing therapeutic strategies. By targeting specific components of the UPR, it may be possible to mitigate disease progression and restore cellular function. This article concludes by identifying key areas for future research and emphasizing the potential of UPR-modulating agents as novel therapeutic interventions.

Endoplasmic reticulum stress, Unfolded protein response (UPR), Protein homeostasis, Cellular dysfunction

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