Nuclear Dbf2-related protein (Ndr2) is a serine/threonine kinase in the subgroup of the AGC family kinases and a core member of the Hippo signaling. Ndr2 plays a key role in the differentiation and maturation of neurons, regulating dendritic and axonal growth through integrin receptors. Further work from our lab has demonstrated that the deletion of Ndr2 kinase can improve spatial memory in old mice (see presentation by Miguel del Angel). Moreover, analysis of the hippocampal proteome revealed a differential expression of GAP43 protein in aged Ndr2 KO mice compared to wild type (WT) mice. While GAP43 protein expression decreases in the WT dorsal hippocampus proteome during aging, Ndr2 KO mice display overall increased GAP43 levels and a reduced decline. GAP43, also known as neuromodulin, is a membrane protein associated with neuronal outgrowth, neurogenesis, and plasticity, and has been identified as a target gene of the YAP, a key downstream transcription factor of Hippo pathway. Reduction of GAP43 expression in the dorsal hippocampus was confirmed in aged male, but not in aged female mice. Further analysis of the brains via immunohistochemistry revealed that the reduction of GAP43 during aging varies across different subregions of the dorsal hippocampus. We are currently investigating the role of Ndr2 kinase altered GAP43 expression in hippocampus during aging and its consequence for maintaining normal hippocampal physiology and hippocampus-dependent behavior.