Taken together our results show that Rab7 and its trimeric Mon1-Ccz1-C18orf8 (MCC) GEF control cellular cholesterol homeostasis through coordinated regulation of LDL trafficking and NPC1-dependent lysosomal cholesterol export, making it a potential therapeutic target in Niemann Pick disease. The gene discussed is RMC1; the disease is Niemann-Pick disease.