Glutamate receptor-interacting protein 2 (GRIP2)

Glutamate receptor-interacting protein 2 (GRIP2) is a neuronal scaffold protein encoded by the GRIP2 gene in humans. GRIP2 is characterized by seven PDZ (PSD-95/Discs large/ZO-1) domains highly homologous to the related protein GRIP1, enabling it to interact with the C-termini of AMPA-type glutamate receptor subunits, particularly GluR2 and GluR3. GRIP2 functions as an adaptor in the postsynaptic density, playing essential roles in the trafficking, clustering, and stabilization of AMPA-type glutamate receptors at excitatory synapses in the central nervous system. It is enriched in postsynaptic densities of neurons, where it modulates synaptic strength and receptor localization, influencing excitatory neurotransmission. GRIP2 operates within large multi-protein complexes, engaging in protein-protein interactions (e.g., with AMPA receptor subunits, ephrins, EPH receptors, and other synaptic scaffolds) to govern the structural and functional organization of the synapse. Alterations in GRIP2 have been linked to neurodevelopmental disorders, such as autism spectrum disorder and Seckel syndrome, potentially through dysregulation of excitatory synaptic transmission. GRIP2 is not itself a therapeutic target or biomarker and there are currently no approved drugs acting directly on this protein. It is best classified functionally as a postsynaptic scaffolding (adapter) protein rather than a receptor, enzyme, or transporter.

Other names

Glutamate receptor-interacting protein 2GRIP2KIAA1719GRIP-2ABP-L (AMPA receptor-binding protein large isoform)pABP-L (palmitoylated splice variant)