In addition, it was discovered that the familial ALS patients exhibit a significant enrichment of additional rare deleterious variants in the exon 4 of GLT8D1, which clusters near the substrate-binding domain of the exon and reduces the enzyme activity of GLT8D1 (Cao et al., 2021; Candelise et al., 2022). This evidence concerns the gene GLT8D1 and amyotrophic lateral sclerosis.