The current authors suggest that irreversible Piezo2 channelopathy induces progressive Kv1.1, Kv1.2, and K2P ion channels dysfunction in DRG neurons that may lead to loss of pressure overload-induced remodeling and to the initiation of the autoimmune mechanism of ALS pathogenesis. The gene discussed is KCNA1; the disease is amyotrophic lateral sclerosis.