In addition, hUPF1, a human homolog ofECM32, rescues FUS/TLS toxicity, as do its interacting partnershUPF2 and (to a lesser extent) hUPF3. Therescue does not involve a decrease in FUS/TLS expression or a change in itslocalization or inclusion formation, but it does depend on intact functional domainsof hUPF1. Since hUPF1 plays an important functionin mRNA quality control, our data raise the possibility that this pathway might beinvolved in the pathogenesis of FUS/TLS-associated ALS, andpossibly of the disease in general. Here, UPF1 is linked to amyotrophic lateral sclerosis.