GRIP1 (glutamate receptor interacting protein 1) functions as a molecular scaffold protein that regulates synaptic plasticity and learning and memory through AMPAR trafficking. Mechanistically, GRIP1 binds to AMPAR subunits, particularly GluA2, and facilitates their insertion into the postsynaptic membrane during long-term potentiation (LTP) 1. This trafficking is regulated by phosphorylation of GluA2 residues, where decreased serine-880 phosphorylation and elevated tyrosine-876 phosphorylation enhance GRIP1-AMPAR binding 1. Beyond glutamate signaling, GRIP1 functions as a coactivator in nuclear receptor signaling, binding beta-catenin and synergistically enhancing transcriptional activation by androgen receptor and other nuclear receptors 2. GRIP1 also regulates glucocorticoid-driven macrophage programming through interaction with KLF4 and the glucocorticoid receptor 3. Disease relevance includes Fraser syndrome 3, a rare autosomal recessive developmental disorder 4. GRIP1 knockout mice exhibit impaired hippocampal LTP and deficits in learning and memory 1, establishing GRIP1 as essential for Hebbian synaptic plasticity. Additionally, GRIP1 regulates GABAAR recycling at inhibitory synapses 5, indicating broader roles in postsynaptic receptor homeostasis across synapse types.