Our recent research findings suggest that the Rhes protein, functioning as a multifunctional GTPase resembling SUMO E3 ligase, plays a vital role in the formation of TNTs and the facilitation of mHTT transportation between striatal medium spiny neurons (MSNs) and the cortex; the brain circuit is known to be highly vulnerable to degeneration in HD [2,4,22,23]. Here, RASD2 is linked to Huntington disease.