RAN and amyotrophic lateral sclerosis: Deriving from the patient pathology showing physical- and colocalization-interaction between MATR3 and G4C2 RNA, and genetic interaction between MATR3 and G4C2, both in vivo and in C9-ALS patient-derived neurons, we suggest two possible ways in which this interaction could be involved in C9-ALS pathobiology: (1) Decreased levels of nuclear MATR3 and/or cytoplasmic localization of MATR3 that could perturb its physiological functions due to alteration in the subcellular distribution; and, (2) nuclear sequestration of G4C2 RNA foci and suppression of RAN translation.