Our data thus suggest that IgG autoantibodies in ALS-T2DM sera immunocapture CaVα2δ1 subunits in the plasma membrane, resulting in a destructive exaggeration of [Ca2+]i followed by its pathological translation into mitochondrial dysfunction, subsequent impairment of insulin secretion, eventual islet cell death, and diabetes. Here, INS is linked to amyotrophic lateral sclerosis.