The mechanisms by which glutamate receptors are concentrated in brain excitatory synapses are believed to involve interactions between receptor subunits and postsynaptic anchoring or scaffolding proteins. Recently GRIP, a protein containing seven PDZ domains, was identified as an AMPA receptor binding protein and implicated in the synaptic targeting of AMPA receptors. Here we show that GRIP mRNA is also expressed in some tissues outside of the brain, including testis and kidney. Specific antibodies were raised to study GRIP protein. On Western blots, GRIP protein appears as a heterogeneous band(similar to 130 kilodaltons) which is expressed in widespread brain regions and throughout postnatal development. Biochemical studies reveal that GRIP is largely membrane associated and enriched in the postsynaptic density (PSD), though not as highly concentrated in the PSD as is PSD-95. By immunohistochemistry, GRIP is distributed in a somatodendritic pattern in neurons of adult rat brain, with especially prominent expression in a subset of interneurons. (C) 1998 Elsevier Science Ltd. All rights reserved.