HTT and Huntington disease: mHTT-induced neurodegeneration in HD likely involves loss-of-function phenotypes associated with HTT protein misfolding and sequestration in insoluble aggregates, and gain-of-toxic functions caused by dysregulation of protein-protein interactions or post-translational modifications, and/or disruption of key pathways that regulate cell homeostasis and survival (Ratovitski et al., 2012).