Studies performed in neuronal cultures prepared from YAC128 mice, a model to study Huntington’s disease, showed a decrease in the HIP14L-mediated palmitoylation of GluN2B, specifically on Cysteine cluster II, which was associated with an upregulation in extrasynaptic GluN2B-containing NMDAR in striatal neurons. This evidence concerns the gene GRIN2B and juvenile Huntington disease.