Previous reports on TBK1 mutations in ALS49, 50 and the recently identified interaction of the putative Rab GTPase GEF chromosome 9 open reading frame 72 (C9ORF72) with WD repeat-containing protein 41 (WDR41) and Smith-Magenis syndrome chromosomal region candidate gene 8 protein (SMCR8)51 support the idea that impaired autophagy could make major contributions to the pathophysiology of motoneuron disease. The gene discussed is TBK1; the disease is Smith-Magenis syndrome.