This region of the protein is particularly interesting within the context of SOD1 aggregation and prion-like propagation as: (i) it contains few ALS-associated mutations compared to the rest of the amino acid sequence, (ii) it nevertheless has high sequence divergence from murine SOD1 (murine SOD1 does not co-aggregate with human SOD1 or become misfolded in murine models [15,28]) and (iii) it contains the sole tryptophan in SOD1 which plays a key role in SOD1 aggregation and prion-like propagation [15,29,30]. Here, SOD1 is linked to amyotrophic lateral sclerosis.