GRIN2B and Huntington disease: This is the first study, to our knowledge, to show that: (i) altered palmitoylation on cluster II of GluN2B regulates extrasynaptic surface expression in striatal neurons; (ii) the increase in GluN2B-containing NMDAR extrasynaptic localization and function previously found in a variety of HD mouse models (Milnerwood et al., 2010; Botelho et al., 2014; Plotkin et al., 2014) may be linked to a reduction in palmitoylation on cluster II of GluN2B (Figure 1, 2, 4).