Together, these findings not only expand the repertoire of C9orf72 G4C2 G4 folding structures and topologies, but also provide new mechanistic insights into the conformational plasticity of G4C2 repeats and lay a structural foundation for the rational design of therapeutic agents targeting C9orf72-linked ALS and FTD. This evidence concerns the gene C9orf72 and frontotemporal dementia.