Recently, Nikolaev and colleagues[10] reported that the N-terminal fragment of amyloid precursor protein (N-APP) may act as a ligand of DR6 and trigger axon pruning and neurodegeneration via caspase 6, suggesting a role for this receptor in the neurodegeneration observed in Alzheimer’s disease (AD; for review see[11]). The gene discussed is TNFRSF21; the disease is Alzheimer disease.