Cystinosin (CTNS) (CTNS)

Cystinosin (CTNS) is a seven-transmembrane protein located in the lysosomal membrane that functions as a proton-driven symporter to export cystine, the oxidized dimer of cysteine, from the lysosomal lumen to the cytosol. It is the primary protein defective in cystinosis, a rare autosomal recessive lysosomal storage disorder characterized by the systemic accumulation of cystine crystals. This accumulation leads to progressive multi-organ damage, most notably causing renal Fanconi syndrome and eventual kidney failure, as well as ocular complications like corneal crystal deposition. While the current standard of care, cysteamine, reduces lysosomal cystine by providing an alternative exit pathway, it does not cure the underlying genetic defect and is associated with significant side effects and dosing challenges. Emerging therapeutic approaches, such as autologous hematopoietic stem cell gene therapy (e.g., DFT383), aim to restore functional CTNS expression to provide a long-term solution. Beyond its transport function, cystinosin also plays a role in regulating mTORC1 signaling, lysosomal dynamics, and melanin synthesis, highlighting its broader importance in cellular homeostasis.

Other names

CTNSPQLC4SLC66A4CTNS-LSBCystinosin, lysosomal cystine transporter

Cysteamine reacts with intralysosomal cystine to form a cysteine-cysteamine mixed disulfide that exits the lysosome via the PQLC2 transporter, bypassing the defective cystinosin. Gene therapy (DFT383) delivers a functional copy of the CTNS gene to restore natural cystine-proton symport activity.