The ubiquitinated inclusions of pathological TDP-43 accumulation in motor neurons found in sporadic ALS and in C9orf72 G4C2-repeat ALS, as well as other specific proteinopathies, as in SOD1- and FUS-related ALS, suggest that cytosolic proteinopathy is the initial pathological marker, developing long before the transition to overt ALS [14]. Here, C9orf72 is linked to proteostasis deficiencies.