Niemann‐Pick disease type C (NPC) is a rare autosomal recessive metabolic disorder caused by the deficient function of either of two proteins, named NPC1 and NPC2, resulting from mutations in the corresponding (NPC1 and NPC2) genes. Genotype–phenotype studies have generally shown a good correlation between two alleles with stop, nonsense, or frameshift mutations and the most severe neurologic course. The consequences of NPC1 or NPC2 mutations are well documented, including variable enlargement of the liver and spleen, with foam cell infiltrates and sea blue histiocytes in the spleen, liver, and bone marrow. At the cellular level, the pathogenic cascade in NPC is remarkably complex and incompletely understood. Cholesterol binding to the sterol sensing domain is needed for an ordered structure of the NPC1 protein in keeping with the cholesterol regulation of contact site function. In the perinatal period and early infancy, NPC presents with visceral manifestations, NPC is a progressive neurodegenerative disease.