Mutations in the CTNS gene encoding the lysosomal membrane cystine transporter cystinosin are the cause of cystinosis, an autosomal recessive lysosomal storage disease. More than 140 CTNS mutations have been reported worldwide. Recent studies have discovered that cystinosin exerts other key cellular functions beyond cystine transport such as regulation of oxidative state, lysosomal dynamics and autophagy. Here, we review the different mutations described in the CTNS gene and the geographical distribution of incidence. In addition, the characteristics of the various mutations in relation to the functions of cystinosin needs to be further elucidated. In this review, we highlight the functional consequences of the different mutations in correlation with the clinical phenotypes. Moreover, we propose how this understanding would be fundamental for the development of new technologies through targeted gene therapy, holding promises for a possible cure of the kidney and extra-renal phenotypes of cystinosis.

sponsorship: E.L. is supported by FWO (1801110N) and E-RARE (JTC2014). R.G is supported by FWO (G0B3516N). E.L., R.G., and S.P.B. are supported by C1 grant from KU Leuven. F.O.A. is supported by FWO (12Q9917N). (FWO|1801110N, FWO|G0B3516N, FWO|12Q9917N, E-RARE (JTC), C1 grant from KU Leuven)