ALS2 and amyotrophic lateral sclerosis: Although the levels of the ALS-related neuronal intermediate filament proteins [peripherin and neurofilament heavy chain (NFH)] [35] and the ALS-causative gene product [TAR DNA-binding protein 43-kD (TDP-43)] [1], [2] were unchanged, a progressive accumulation of insoluble high-molecular weight (HMW) SOD1 and poly-ubiquitinated proteins was observed in mice expressing SOD1H46R, particularly in those lacking ALS2 (Als2−/−;SOD1H46R) (Figure 4, S5B, S5C, S5E, S6A, and S6B).