Postsynaptic Density protein 95 (PSD95), also known as Synapse associated protein 90kDa, is a member of the membrane-associated guanylate kinase (MAGUK) family of proteins. PSD95 is a scaffolding protein and is involved in the assembly and function of the postsynaptic density complex (1).  These family members consist of an N-terminal variable segment followed by three amino-terminal PDZ domains, an upstream SH3 domain and an inactive carboxyl-terminal guanylate kinase (GK) domain. The first and second PDZ domain localize NMDA receptors  and K+ channels to synapses, and the third binds to neuroligins which are neuronal cell adhesion molecules that interact with b-neurexins and form intercellular junctions.  PSD-95 also binds to neuronal nitric oxide synthase, possibly through interactions between PDZ domains present on both proteins (2). Thus different PDZ domains of PSD-95 might be specialized for distinct functions (3, 4).

PSD95 participates in synaptic targeting of AMPA receptors through an indirect manner involving Stargazin and related transmembrane AMPA receptor regulatory proteins (TARPs) (5). The protein is implicated in experience dependent plasticity and plays an indispensable role in learning (6). Mutations in PSD95 are associated with autism (7).