E2F1 and amyotrophic lateral sclerosis: Alterations in the RB1/E2F1 pathway have been observed in ALS neurons in vivo and are thought to contribute to neuron cell death in this disorder.70,71 Our data provide direct evidence that p97 disease mutants affect the cell cycle in mature MNs and indicates that cell cycle activation may be a cause of p97R155H/+-linked MN death.