SORT1 and HIV-associated neurocognitive disorder: Most notably, our study identifies that gp95-stimulated NMDARs activate the nNOS-cGMP-cGKII pathway, which subsequently phosphorylates IP3Rs and AMPAR subunit GluA1, leading to the elevation of surface GluA1 expression and AMPAR-mediated synaptic activity, a cellular basis of synaptic dysfunction in HAND (Fig 8).