The PICK1‐GluA2 protein–protein interaction leads to the trafficking of AMPA type receptor away from the neuron surface through endocytosis, thereby reducing synaptic communication.6, 7 We proposed to develop an inhibitor targeting the PICK1 PDZ domain‐GluA2 interaction using structure‐aided drug design for the treatment of neurodegenerative diseases through the stabilization of surface AMPA type receptors on neurons. Here, PICK1 is linked to neurodegenerative disease.