Glutamate receptors mediate most excitatory neurotransmission in the brain and play an important role in neural plasticity, neural development and neuro-degeneration. The glutamate receptor interacting proteins, GRIP1 and GRIP2, are members of the PDZ domain-containing protein family, and they specifically bind to the carboxy-terminus of AMPA receptor subunits, GluR-2 and GluR-3. GRIP1 and GRIP2 are involved in the targeting of GluR-2 and GluR-3 to the synapse. GRIP1 and GRIP2 are widely expressed in brain, with the highest levels in the cerebral cortex, hippocampus and olfactory bulb. They are both enriched in synaptic plasma and postsynaptic density fractions. GRIP1 is expressed in early development before the expression of AMPA receptors, specifically postnatal days 8-10, while GRIP2 expression parallels that of AMPA receptors during later developmental stages. GRIP1 and GRIP2 may mediate the endocytotic rate of GluR-2 and GluR-3 in response to the phosphorylation of the receptors on Ser 880 by PKC, which is implicated in the induction of cerebellar long-term depression (LTD).