As an etiologic and essential biofactor that can provoke a ceramide deficiency even under the normal ceramide metabolism observed in the AD skin [9,10], we have discovered a novel enzyme, sphingomyelin (SM) deacylase, which cleaves the N-acyl linkage of SM and glucosylceramide [4,9,11,12,13] by competing with acid sphingomyelinase and β-glucocerebrosidase to yield their lysoforms sphigosylphosphorylcholine (SPC) and glucosylsphingosin (GS), respectively, instead of ceramide, resulting in the ceramide deficiency in AD skin. The gene discussed is SMPD1; the disease is Alzheimer disease.