Mutations in NPC1, which encodes a cholesterol-binding protein related to the Hedgehog receptor Patched, can cause Niemann-Pick type C (NPC)disease, a neurodegenerative disorder characterised by the abnormal cellular accumulation of lipids. Huang and colleagues now describe a Drosophila model of NPC disease in which mutating the NPC1-like gene dnpc1a disrupts moulting and sterol homeostasis (see ). Sterol accumulates throughout dnpc1a mutants in a punctate fashion, as in NPC disease. Moulting in mutant flies is restored by feeding them with the steroid moulting hormone ecdysone or its precursors, or by expressing dnpc1a in the ring gland, which normally makes ecdysone. The researchers propose that dNPC1a and NPC1 ensure that sufficient intracellular cholesterol is available for steroid hormone biosynthesis, and suggest that NPC disease is a sterol shortage disease, and not a sterol excess disease as previously thought.
