To recapitulate increased soluble Aβ observed in DS forebrains and explore the impact of BACE2 on Aβ cleavage, Alic et al. reprogram iPSCs from primary keratinocytes of the same DS patient mosaic for T21 and normal disomy 21 cells and create isogenic T21 and disomic 21 (D21) iPSC lines [101]. The gene discussed is BACE2; the disease is Dravet syndrome.