A Rare Kidney Disease To Cure Them All? Towards Mechanism-Based Therapies for Proteinopathies

Moran Dvela-Levitt, Jillian L. Shaw, Anna Greka

Research output: Contribution to journalReview articlepeer-review

4 Scopus citations


Autosomal dominant tubulointerstitial kidney diseases (ADTKDs) are a group of rare genetic diseases that lead to kidney failure. Mutations in the MUC1 gene cause ADTKD-MUC1 (MUC1 kidney disease, MKD), a disorder with no available therapies. Recent studies have identified the molecular and cellular mechanisms that drive MKD disease pathogenesis. Armed with patient-derived cell lines and pluripotent stem cell (iPSC)-derived kidney organoids, it was found that MKD is a toxic proteinopathy caused by the intracellular accumulation of misfolded MUC1 protein in the early secretory pathway. We discuss the advantages of studying rare monogenic kidney diseases, describe effective patient-derived model systems, and highlight recent mechanistic insights into protein quality control that have implications for additional proteinopathies beyond rare kidney diseases.

Original languageEnglish
Pages (from-to)394-409
Number of pages16
JournalTrends in Molecular Medicine
Issue number4
StatePublished - Apr 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2020 Elsevier Ltd


  • MUC1 kidney disease
  • P24
  • TMED
  • autosomal dominant tubulointerstitial kidney disease (ADTKD)
  • cargo quality control
  • chronic kidney disease
  • proteinopathies
  • rare diseases


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