The expanded polyglutamine tract in mutant huntingtin causes the protein to misfold and aggregate inside neurons, forming inclusion bodies that are a pathological hallmark of HD. The cell's main system for clearing such large, aggregate-prone proteins — macroautophagy — is itself impaired in HD patient neurons and animal models, creating a vicious cycle where the clearance system needed to remove the toxic protein is disabled by that same protein. Recent preclinical work has identified small molecules that can re-engage autophagy-lysosomal clearance pathways (for example, via modulation of the p75 neurotrophin receptor) and reduce huntingtin aggregate burden in cellular and mouse models, offering a possible future complement to huntingtin-lowering approaches.