This model led to three crucial observations: (1) RBM20 R636S HMZ mutation leads to highly penetrant neonatal lethality due to heart failure; (2) mutant RBM20 co-localizes with stress granules in the CM cytoplasm after metabolic stress induced by sodium arsenate; and (3) RBM20 undergoes an apparent liquid–liquid phase separation. Here, RBM20 is linked to heart failure.