The functional relevance of these findings is further validated by (1) the neuroprotection observed upon reduction of the single Drosophila PIAS (dPIAS), which is most similar to PIAS1 (Hari et al., 2001), in flies expressing a mutant fragment of HTT, and (2) the profound accumulation of SUMO-2-modified HMW protein in human HD brain. This evidence concerns the gene PIAS1 and Huntington disease.