Molecular Mechanisms and Treatment Options of Nephropathic Cystinosis

Trends Mol Med. 2021 Jul;27(7):673-686. doi: 10.1016/j.molmed.2021.04.004. Epub 2021 May 8.


Nephropathic cystinosis is a severe, monogenic systemic disorder that presents early in life and leads to progressive organ damage, particularly affecting the kidneys. It is caused by mutations in the CTNS gene, which encodes the lysosomal transporter cystinosin, resulting in intralysosomal accumulation of cystine. Recent studies demonstrated that the loss of cystinosin is associated with disrupted autophagy dynamics, accumulation of distorted mitochondria, and increased oxidative stress, leading to abnormal proliferation and dysfunction of kidney cells. We discuss these molecular mechanisms driving nephropathic cystinosis. Further, we consider how unravelling molecular mechanisms supports the identification and development of new strategies for cystinosis by the use of small molecules, biologicals, and genetic rescue of the disease in vitro and in vivo.

Keywords: CTNS gene; cystinosis; lysosomal storage disorder; renal Fanconi syndrome; therapeutic strategies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Transport Systems, Neutral / genetics*
  • Cystinosis / genetics
  • Cystinosis / pathology
  • Cystinosis / therapy*
  • Genetic Therapy / methods*
  • Humans
  • Mutation*
  • Small Molecule Libraries / therapeutic use*


  • Amino Acid Transport Systems, Neutral
  • CTNS protein, human
  • Small Molecule Libraries