A remarkable splicing change in the polymerase delta interacting protein 3 (POLDIP3) as a result of TAR DNA binding protein (TDP-43) depletion in two types of cultured cells POLDIP3 (variant-1) decreased and POLDIP3 lacking exon 3 (variant-2) increased in cells treated with TDP-43 siRNA. POLDIP3 variant-2 mRNA was found to be increased in motor cortex, spinal cord, and spinal motor neurons collected by laser capture microdissection in patients with ALS. This evidence concerns the gene POLDIP3 and amyotrophic lateral sclerosis.