GRIP2 (glutamate receptor interacting protein 2) functions as a PDZ domain-containing scaffold protein that mediates AMPA receptor trafficking and synaptic plasticity in neurons. GRIP2 binds to the C-termini of AMPA receptor subunits GluA2 and GluA3 1 and interacts with the exocyst protein complex to regulate activity-dependent AMPA receptor recycling 1. This trafficking function is critical for excitatory synaptic transmission and neuronal plasticity. In Alzheimer's disease models, GRIP2 expression is downregulated alongside other synaptic proteins; HDAC inhibitors restore GRIP2 expression and rescue synaptic damage and neuronal loss through enhanced AMPA receptor signaling 2. Beyond its canonical neuronal role, GRIP2 has emerged as a component of cuproptosis-related gene signatures with prognostic significance in ovarian cancer 3 and oral squamous cell carcinoma 4, though the mechanistic basis for these associations remains unclear. GRIP2 also interacts with viral proteins: Tick-borne encephalitis virus NS5 protein targets GRIP2 through PDZ binding motifs, affecting viral replication 5. Additionally, GRIP2 expression is upregulated in type 2 diabetes patients 6, suggesting broader metabolic roles. Overall, GRIP2 serves as a critical regulator of glutamatergic synaptic function with emerging roles in cancer biology and metabolic disease.