Familial and sporadic ALS share common pathogenetic mechanisms, including (i) aggregation of misfolded or mutated proteins, most commonly SOD1, TDP-43 and FUS, causing neurodegeneration directly or through activation of detrimental neuroinflammatory response; (ii) alteration of nuclear RNA transport, resulting in neurotoxicity due to perturbation of gene splicing and sequestration of RNA-binding proteins within the nucleus; (iii) impairment of cytoskeletal dynamics affecting axonal stability, transport and growth [79]. The gene discussed is FUS; the disease is amyotrophic lateral sclerosis.