Under normal physiological condition, mTOR regulates varied biological processes that are crucial for neuronal function and survival. In HD, mHTT disrupts mTORC1 function by direct interaction with mTOR, causing neuronal dysfunction by negatively impacting multiple pathways. In the striatum, mHTT further impairs mTORC1 activity by interfering with Rhes, a striatum enriched mTOR regulator. Thus, a concomitant loss of Rhes and mTORC1 activity may render striatal tissue vulnerable to early degeneration in HD.