Guided by this hypothesis, our current study has demonstrated that RIN3 expression was significantly increased in neurons of APP/PS1 mice; RIN3 interacted with BIN1/CD2AP to regulate APP trafficking and processing; Increased levels of RIN3 significantly impacted endocytic trafficking process and APP cleavage, that may lead to neuronal degeneration in early AD pathogenesis. Here, RIN3 is linked to Alzheimer disease.