The increase in SOC pathway activity in HD may be caused directly by an increase in STIM2 expression in the presence of mHTT (Wu et al., 2016) or may result from a compensatory response of cells to the destabilization of Ca2+ signaling, such as an increase in the activity of IP3R1 by mHTT in YAC128 mice (Tang et al., 2003, 2004; Wu et al., 2016) or the modulation of SOC channels by receptors in the ER, such as S1Rs (Su et al., 2010). This evidence concerns the gene ITPR1 and Huntington disease.