PIAS1 affects the accumulation of mHtt in HD by modulating the levels of SUMO‐modified proteins, including Htt. PIAS1 appears to function at the protein homeostasis level rather than modulating Htt gene expression directly, influencing PTMs of proteins like Htt, Tau, and α‐syn, which are linked to regulating their abundance and association with cellular clearance networks. This evidence concerns the gene HTT and Huntington disease.