We observed that knocking down endogenous MATR3 resulted in a significant decrease in the percentage of neurons that exhibit G4C2 foci (Fig. 6b), and simultaneously, the number of G4C2 foci per individual neuron (Fig. 6a–c), consistently across two independent patient-derived C9-ALS iPSC MNs (Fig. 6b), confirming a disease-specific genetic interaction between MATR3 and G4C2 repeat RNA in these neurons. Here, MATR3 is linked to amyotrophic lateral sclerosis.