The FERM and PDZ domain containing (FRMPD) protein family consists of four proteins that contain a FERM (Four-point-one, erzin, radixin, moesin) domain and at least one PDZ (PSD-95/Discs large/Zonula-occuldens-1) domain. FRMPD4, also known as Preso, also contains another protein interaction domain termed WW (domain with two conserved Trp residues) at its amino terminus. It was identified through a yeast two-hybrid screen using the PDZ domain of PSD-95 as bait and is highly expressed in multiple regions of the brain and is enriched in the postsynaptic density (PSD) fractions. Overexpression of FRMPD4 in cultured hippocampal neurons significantly increased the linear density of dendritic spines without changing their length and width; conversely, knockdown experiments using RNAi caused a decrease in spine density, indicating FRMPD4 positively regulates dendritic spine density but not morphology. The decreased level of FRMPD4 also resulted in reduced levels of excitatory synaptic transmission, suggesting that FRMPD4 is required for maintenance of excitatory synaptic transmission.