SMPD1 and Onset: Several clear examples are provided by recent publications, which show that cholesterol mediated activation of acid sphingomyelinase leads to the increase in cellular ceramide,53 which triggers aberrant endosome biogenesis resulting in increased C3a internalization, aberrant mTORC1 activation, and decreased autophagosome biogenesis in RPE cells of an Abca4−/− mouse model of Stargardt early onset with macular degeneration.54