PML also protects the pathogenic ALS-associated variants TDP-43P112H or TDP-43K263E from aggregation, which become highly insoluble under stress in the absence of rapamycin but can be kept in the soluble fraction in the presence of rapamycin (Fig. 5e and Extended Data Fig. 6d). The gene discussed is PML; the disease is amyotrophic lateral sclerosis.