We examined whether Phe-induced hyperactivation of GluN2B affects tonic inhibition in PKU mice, based on the evidence that overexpression and suppression of GluN2B in cultured hippocampal neurons results in decreased and increased tonic inhibition, respectively, through the regulation of trafficking of the GABAAR α5 subunit (α5-GABAAR) (40). The gene discussed is GRIN2B; the disease is phenylketonuria.