The found charge-altering variants of SDC3, and the variants of KCNA2, KCNK1, KCNK16, and HSF1 are not only interesting in terms of the downstream progressive die-back initiating pathomechanistic pathway, but might highlight the hierarchical degradation and depletion of ion channels and proteins on route to ALS onset. Here, HSF1 is linked to amyotrophic lateral sclerosis.