<p>Septin-3 and Septin-5 are components of the septin cytoskeleton highly expressed in the nervous system, yet the extent of their shared and distinct roles is not fully understood. We recently demonstrated that Septin-3 regulates late-phase long-term potentiation (L-LTP)-dependent invasion of smooth endoplasmic reticulum (sER) into dentate gyrus (DG) spines. <i>Septin3</i>^−/− mice exhibit normal synaptic ultrastructure in the hippocampal DG, CA3, and CA1, yet the fraction of sER-containing spines is reduced; behaviorally, they show selective deficits in 1-day object recognition and 1-day contextual fear memory, whereas cued fear conditioning and contextual memory tested at 1&#xa0;month are intact. Here, using adult male <i>Septin5</i>^−/− mice, we tested whether morphological and behavioral phenotypes identified in <i>Septin3</i>^−/− mice are shared or subunit-specific. Electron microscopy showed no detectable differences in synapse density, spine volume, and postsynaptic density (PSD) area in the hippocampal DG, CA3, and CA1, with an unchanged fraction of sER-containing spines relative to wild-type littermates. Behaviorally, <i>Septin5</i>^−/− mice were impaired in recent (1&#xa0;day) and remote (1&#xa0;month) contextual fear memory, but were normal in 1-day novel object recognition memory and in recent and remote cued fear memory. The shared and distinct structural and behavioral phenotypes observed in <i>Septin5</i>^−/− and <i>Septin3</i>^−/− mice suggest either sER-independent common mechanisms or subunit-specific ones for recent contextual fear memory deficit, and indicate a Septin-5-dependent contribution to remote contextual fear memory.</p>