Many cellular, invertebrate and vertebrate models of TDP-43 proteinopathy, based on the expression of full length, mutated, truncated or mislocalised protein, have been developed since the first reports emerged of the neuropathological and genetic role of this protein in FTLD-U, ALS and many other neurodegenerative diseases [5], [28]–[30]. This evidence concerns the gene TARDBP and neurodegenerative disease.