Endoplasmic reticulum-associated biomarkers for molecular phenotyping of rare kidney disease

The endoplasmic reticulum (ER) is the central site for folding, post-translational modifi-cations, and transport of secretory and membrane proteins. An imbalance between the load of mis-folded proteins and the folding capacity of the ER causes ER stress and an unfolded protein re-sponse. 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.