Upregulation of α2δ-1 protein is of importance in the development of neuropathic pain,24–27 and α2δ-1 is also the drug target for gabapentinoid drugs used in neuropathic pain.28,29 These drugs inhibit calcium channel trafficking when applied chronically.14,18 In the present study, we have examined the nature of the enzyme(s) involved in proteolytic cleavage of α2δ subunits, since inhibition of its proteolytic cleavage could represent a novel point of therapeutic intervention. Here, ATXN2L is linked to neuropathic pain.