To understand the relationship of Fpn loss with AD-like pathological/behavioral phenotypes, we generated a mouse strain with selective knockout of Fpn in the excitatory neurons of the hippocampus and neocortex and found that Fpnfl/fl/NEXcre mice developed obvious hippocampal atrophy and memory impairments, as seen in AD. Here, SLC40A1 is linked to Alzheimer disease.