ONLINE COVER This week, Zhang et al. report a regulatory loop between the intracellular domain of the amyloid precursor protein and the kinase LRRK2. The loop promoted neuronal loss and other disease markers in mouse models of Parkinson’s disease that were reduced with the APP-processing inhibitor itanapraced. The image shows staining for markers of autophagy (green) and dopaminergic neurons (red) in brain tissue from LRRK2-mutant mice.