Endoplasmic Reticulum-Associated Biomarkers for Molecular Phenotyping of Rare Kidney Disease

The endoplasmic reticulum (ER) is the central site for folding, post-translational modifications, and transport of secretory and membrane proteins. An imbalance between the load of misfolded proteins and the folding capacity of the ER causes ER stress and an unfolded protein response. Emerging evidence has shown that ER stress or the derangement of ER proteostasis contributes to the development and progression of a variety of glomerular and tubular diseases. This review gives a comprehensive summary of studies that have elucidated the role of the three ER stress signaling pathways, including inositol-requiring enzyme 1 (IRE1), protein kinase R-like ER kinase (PERK), and activating transcription factor 6 (ATF6) signaling in the pathogenesis of kidney disease. In addition, we highlight the recent discovery of ER-associated biomarkers, including MANF, ERdj3, ERdj4, CRELD2, PDIA3, and angiogenin. The implementation of these novel biomarkers may accelerate early diagnosis and therapeutic intervention in rare kidney disease.