In a minority of ALS and/or FTLD cases, cytoplasmic aggregation of TDP-43 and its loss from the nucleus is associated with pathogenic mutations in the genes encoding TDP-43 (TARDBP[50]), progranulin (PGRN [33]), valosin containing protein (VCP[42]) and Ubiquilin 2 (UBQLN2 [10]). Here, GRN is linked to amyotrophic lateral sclerosis.