Neurons don't appreciate FUSsing in the cytoplasm.

In the amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) neurodegeneration field, two nuclear factors (first TDP-43, then FUS) have recently made researchers realize that alterations at the level of hnRNP proteins and RNA metabolism may have a decisive function in disease origin and progression. However, the exact mechanisms through which this occurs are still largely unknown. In this issue of The EMBO Journal, Dormann et al have for the first time succeeded in linking ALS-associated mutations in the FUS protein with a specific functional property, that is alterations in nuclear import and stress granule formation. This finding has profound implications for future research efforts in better understanding the pathogenesis mediated by these proteins and eventually developing disease-modifying therapies. [ABSTRACT FROM AUTHOR]