APP and Dravet syndrome: Endogenous APP-βCTF at modestly elevated levels in DS mouse models enlarges early endosomes, impairing neurotrophic function via retrogradely transported signaling endosomes (Salehi et al., 2006; Xu et al., 2016) and early degeneration of BFCNs (Jiang et al., 2016, 2022; Fig. 6).