Although the function of the protein encoded by C9orf72 is still unknown, there are several theories regarding how the C9orf72 repeat expansion leads to ALS and FTD [34] (Figure 1): i) loss of C9orf72 protein expression could inhibit autophagy and promote neuroinflammation (Figure 1A) [35,36]; ii) expanded sense and antisense RNA, derived from the expanded gene, form toxic RNA foci that sequester RNA binding proteins, impairing RNA metabolism (Figure 1B) [15,36]; iii) non-canonical repeat-associated non-ATG (RAN) translation of toxic dipeptide repeat proteins aggregates (Figure 1C) [37]. This evidence concerns the gene C9orf72 and amyotrophic lateral sclerosis.