As one of the earliest identified synaptic abnormalities to occur in HD mice is the overexpression of GluN2B-containing extrasynaptic NMDARs that are preferentially coupled to cell-death pathways (Okamoto et al., 2009; Milnerwood and Raymond, 2010; Milnerwood et al., 2010; Parsons and Raymond, 2014), reduced GluN2B cluster II palmitoylation and subsequent NMDAR mislocalization may play a key role in early HD synaptic dysfunction. Here, GRIN2B is linked to Huntington disease.