In line with the argument that impaired autophagy/mitophagy as a driver of ALS, pharmacological or genetic up-regulation of the SIRT1/NAD+-mitophagy axis alleviates disease phenotypes in ALS mice and ALS patients (Blacher et al., 2019; de la Rubia et al., 2019; Lautrup et al., 2019). The gene discussed is SIRT1; the disease is amyotrophic lateral sclerosis.