The nucleus-VAPB link has important implications, because defects in the nuclear envelope, delocalisation of nuclear pore proteins, and impaired nucleo-cytoplasmic transport, have all been linked to ALS pathogenesis [167,168], and defective nucleo-cytoplasmic transport has been observed in cultured fibroblasts of an ALS8 patient [14]. This evidence concerns the gene VAPB and amyotrophic lateral sclerosis type 8.