The pathogenicity of SPG7 variants p.(G349S) and p.(A510V) described in ALS patients here and previously [26, 27] was further confirmed by yeast complementation assay, showing a diminished proteolytic activity of a protein complex composed of paraplegin harboring these amino acid changes and a proteolytically inactive binding partner, AFG3L2 [28]. The gene discussed is AFG3L2; the disease is amyotrophic lateral sclerosis.