This technology includes compounds that improve endoplasmic reticulum-lysosomal trafficking and normalizes the Niemann-Pick type C (NPC) phenotype in assays using NPC1 patient cells, which can be used for the treatment of NPC, other lysosomal storage disorders, and potentially other neurodegenerative disorders. NPC is a rare neurodegenerative lipidosis caused by mutations in NPC1 or NPC2 genes, and characterized by the accumulation of cholesterol and glycolipids in the late endosomes and lysosomes. Currently there is no FDA-approved treatment for this devastating neurodegenerative disease. Overexpression of such mutant NPC1 proteins has been shown to rescue the disease phenotype in vitro, suggesting that upregulation of endogenous NPC1 as a therapeutic strategy.