The hexanucleotide repeat, r(G4C2) exp , harbored in intron 1 of chromosome 9 open reading frame 72 (C9orf72) mRNA causes genetically defined amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (c9ALS/FTD) . C9orf72 mRNA is bidirectionally transcribed producing repeat expansions in both the sense, r(G4C2) exp , and antisense, r(C4G2) exp , strands that contribute to disease (Figure ). r(G4C2) exp adopts multiple structures, including Gquadruplexes and hairpin structures , the latter of which contains an array of 1×1 G/G internal loop conformations (Figure ). It has been shown that 1×1 G/G internal loops are very dynamic and can interconvert between syn-anti and anti-syn (syn-anti ↔ anti-syn) .