By binding the PTB domain of APPL1, βCTF recruits APPL1 to endosomes, where it stabilizes active GTP-rab5 and increases rab5 activity on endosomes, leading to pathologically accelerated endocytosis, followed by AD-like endosome swelling and selectively impaired axonal transport of endosomes in neurons. Here, APPL1 is linked to Alzheimer disease.