In previous work, we have shown that reduction in DREAM protein levels or blockade of DREAM activity, using repaglinide, activates ATF6 processing which results in a neuroprotective effect in murine models of Huntington’s disease, delaying the onset and the progression of motor and cognitive decline in these mice (Naranjo et al., 2016; López-Hurtado et al., 2018). Here, ATF6 is linked to Mental deterioration.