Cystinosis is an hereditary disease characterized by the accumulation of cystine in all the cells of the body leading to cell death and tissue degeneration such as kidneys, liver, eyes, muscle and brain. We showed that healthy hematopoietic stem cells (HSCs), which are naturally available in the body, can rescue this disease in the mouse model of cystinosis and we are currently developing a clinical trial that allows the patients’ own stem cells to be isolated, corrected for the genetic defect and reintroduced in the patients to stimulate healing. This review report the overall preclinical data that support the clinical translation of the stem cell gene therapy approach for cystinosis and how HSPC transplantation could be an effective one-time treatment to treat cystinosis but also other LSDs associated with a lysosomal transmembrane protein dysfunction.