As the symptoms and TDP-43 pathology in ALS and FTD seemingly follow the anatomical connections [81, 82], it is tempting to speculate that chronic axonal damage triggers TDP-43 relocalization to axons and promotes fibril formation as demonstrated by the maturation within the RNP (ribonucleoprotein) hydrogel. The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.