We successfully overcame both limitations by using the Tat-RACK1 peptide, which by disrupting NR2B/RACK1 interactions, enhances the phosphorylation and activity of NR2B.34 The finding that Tat-RACK1 enhanced extinction without affecting depression-related behavior also showed that discrete NR2B/RACK1-mediated mechanisms contribute to fear versus mood regulation. Here, RACK1 is linked to major depressive disorder.