Niemann-Pick C (NPC) disease is a rare recessive lipidosis marked by excessive accumulation of LDL-derived free cholesterol and glycosphingolipids in the late endosomal-lysosomal (E-L) system. Here we report that ectopic expression of human telomerase reverse transcriptase (hTeRT) in human cells leads to an upregulation of the small GTPase Rab9 and its effector p40. Expression of hTeRT in NPC1 cells results in a correction of their cellular phenotype, including clearance of accumulated cholesterol from their E-L system. Specifically, in NPC1-TeRT cells, the transport of cholesterol from the E-L system to the plasma membrane is restored with a concomitant increase in cholesterol esterification. This effect is Rab9-specific since expression of Rab9 in untransformed NPC1 cells also leads to a reversal of their disease phenotype. These effects are also seen in normal TeRT-immortalized cells and it appears that TeRT expression leads to an increase in the transport of molecules, including cholesterol, from the E-L system, and may play a role in increasing cellular proliferation. These results suggest the existence of alternative endogenous therapeutic targets that can be modulated to reverse the NPC1 disease phenotype.