We found that a deficiency of Car8 either at baseline (genetic variation affecting protein stability and expression as demonstrated in this SCA model)(see Fig. 1), or a Car8 deficiency relative to ITPR1 resulting from inflammation (see Fig. 4), enhances DRG pITPR1, causes increases in cytoplasmic free calcium concentrations, and promotes inflammatory pain behaviors (Figs. 7–9). Here, ITPR1 is linked to autosomal dominant cerebellar ataxia.