HTT and Huntington disease: This observed impairment of the UPS in R6/2 cell synapses [30] coupled with the finding that K48-linked polyubiquitin chains accumulate in R6/2, HdhQ150/Q150 HD knock-in mice and HD patient brains [7] suggests that while UPS impairment can occur as a consequence of mutant htt expression, it is not necessarily a global consequence of mutant htt expression.