Induced human spinal neuron (iSN) models of ALS carrying the GGGGCC hexanucleotide repeat expansion in the C9orf72 gene (C9ALS) display GDE2 abnormalities, TDP-43 dysfunction, and erroneous Wnt activation that, when inhibited, partially rescues TDP-43 molecular function. This evidence concerns the gene GDPD5 and amyotrophic lateral sclerosis.