Such a biphasic change in neuronal activity has been observed in patients with ALS as well as various mouse and hiPSC model systems.9,35,36,52 Interestingly, we found that expression of the AIS master scaffolding protein ankyrin-G (ANK3) and voltage-gated sodium channels Nav1.1 (SCN1A) and Nav1.6 (SCN8A) mirrored this dynamic switch in AIS length and excitability in ALS MNs. This evidence concerns the gene ANK3 and amyotrophic lateral sclerosis.