Postsynaptic density protein 95kD (PSD-95), also known as Synapse associated protein 90kD (SAP90), is a brain specific protein that is highly similar to the Drosophila dlg tumor suppressor protein. PSD-95 is a member of membrane associated proteins that are localized beneath the postsynaptic membrane of synapses in the CNS. PSD-95 contains a carboxyl-terminal guanylate kinase domain, an upstream SH3 domain, and three amino-terminal PDZ domains. PSD-95 interacts with NMDA receptor and Shaker-type K+ channel and contributes to their clustering and localization at the synaptic spines in hippocampal neurons and the pinceau terminal of cerebellar basket cells, respectively. The yeast two hybrid method revealed that the second PDZ domain in PSD-95 binded tightly to the carboxyl terminal (t)-S/TXV sequence of the NR2B subunit of NMDA receptor and of Shaker-type K+ channel. PSD-95 also binds to neuronal nitric oxide synthase, possibly through interaction between PDZ domains present on both proteins.