Finally, a series of rare variants in the HSPB1 and HSPB3 genes have been identified, namely HSPB1-S135A, HSPB3-G67S, HSPB3-R116X [68] and HSPB1-R127W, HSPB1-D149A and HSPB1-T151P [69]; these rare variants are likely pathogenic, and it has been suggested that they may represent a burden in amyotrophic lateral sclerosis (ALS). Here, HSPB3 is linked to amyotrophic lateral sclerosis.