Mutations and deletions in the NPC1 and NPC2 genes cause impaired trafficking of unesterified cholesterol (both low density lipoprotein receptor (LDLR)-internalized and endogenously synthesized) and other lipids (e.g., glycosphingolipids), which accumulate in late endosomes and lysosomes and fail to travel to the plasma membrane and endoplasmic reticulum (ER), resulting in severe cognitive deficits [56], [57]. Here, NPC2 is linked to Cognitive impairment.