The detected upregulation of Sez6, Sez6L and APP cleavage by BACE1 in NPC1 mouse brains, at 4-weeks of age, i.e. early stages in NPC disease pathogenesis [25, 26] is of particular relevance as it implies that enhanced BACE1-dependent cleavage is an early pathological event that precedes neurodegeneration and fully blown disease pathology. The gene discussed is NPC1; the disease is nasopharyngeal carcinoma.