The serine-threonine kinase Ndr2 controls axonal and dendritic growth in vertebrates and invertebrates. Further work from our group has shown that Ndr2 KO mice display deficits in synapse development, and plasticity, that lead to spatial memory impairment. Moreover, the Ndr family of kinases have recently been implicated in the regulation of autophagy, which is essential for memory formation and cognitive function during ageing. Nonetheless, the question of whether Ndr2 is involved in age-related autophagy dysregulation and the cognitive decline associated with it remained. In the current study, we demonstrate that Ndr2 participates in hippocampal neuronal autophagy by regulating the localization of autophagosomes to the synapses. We further show that during ageing, Ndr2 deficiency impairs the autophagic flux and prevents changes in the synaptic proteome of the dorsal hippocampus in pathways associated with neuroinflammation and synaptic transmission. Akin to that, Ndr2 deficiency prevents age-related hippocampal-dependent-memory decline. Finally, we demonstrate that an upregulation of autophagy in the dorsal hippocampus of old mice prevents the protective effect of Ndr2 deficiency in hippocampal-dependent memory. These results demonstrate that Ndr2 participates in the regulation of proteostasis and cognition in the hippocampus and that Ndr2 might be a novel factor with antagonistic pleiotropic functions in the brain during ageing.