SummaryThe concept of Niemann‐Pick disease type C as a secondary sphingomyelin storage disorder (in contrast to the sphingomyelinase‐deficient types A and B) has become more and more prevalent, in view of the complex lipid storage pattern and variable sphingomyelinase activities. Although the primary lesion is still unknown, studies conducted over the past six years have led to a breakthrough by showing that this disorder is characterized by unique abnormalities of intracellular translocation of exogenous cholesterol. In cultured fibroblasts of patients, this block leads to a delayed induction of the homeostatic responses to exogenous cholesterol, in particular cholesteryl ester formation, and to the accumulation of unesterified cholesterol in a vesicular, essentially lysosomal, compartment. The transport of endogenous cholesterol is apparently unaffected. The spectrum of phenotypic heterogeneity in relation to abnormal LDL‐processing has been defined in a large patient population. Clinical presentation of the disease is also reviewed and biochemical correlations are discussed. This discovery has had immediate medical applications, by providing the first strategy for reliable prenatal diagnosis of the disorder and easy diagnosis of patients. To date, the exact implication of the cholesterol transport defect in the pathogenesis of Niemann‐Pick type C is not known; recent observations have opened up new possible approaches for the understanding of this lesion. Although final classification of Niemann‐Pick disease type C must await elucidation of the primary defect(s), present knowledge already establishes that the disease is a nosological entity distinct from Niemann‐Pick disease type A and B, and suggests that it might be the model for a new molecular concept of neurolipidosis — and even of inherited metabolic disease.