Whether and how OPTN affects the NF-κB pathway in ALS is still a controversial issue: OPTN normally suppresses NF-κB activity, and its absence or mutation causes NF-κB translocation to the nucleus and expression of proinflammatory genes involved in neurodegeneration in microglia, neurons, oligodendrocytes and astrocytes [28,29,30,31]. Here, NFKB1 is linked to amyotrophic lateral sclerosis.