Synapse function and plasticity depend on the morphology of dendritic spine. Dendritic filopodium is highly dynamic structure, known as a premature form of the dendritic spine. Here, we report that Phldb2 (pleckstrin homology-like domain, family B, member 2), one binding partner for a well-known actin-cross-linking protein Filamin A, works as a positive regulator of spine maturation. We generated Phldb2-knockout mice and found that a proportion of immature spines (filopodia and thin spines) increased in the hippocampus in vivo, which is consistent with our previous observations with Phldb2 knocked-down cultured hippocampal neurons. Next, we asked whether or not Phldb2 is involved in synaptic plasticity. To address this issue, we employed long-term potentiation (LTP) and Long-term depression (LTD) was induced in hippocampal slices by high frequency stimulation (HFS) and by low frequency stimulation (LFS), respectively. Recording field excitatory postsynaptic potentials (fEPSPs) were abolished in the Phldb2-knockout mice in both LTP and LTD. Therefore, Phldb2 mediates both LTP and LTD in hippocampus.