Fused in Sarcoma (FUS) is a multifunctional DNA/RNA binding protein responsible for vital cellular functions including regulating transcription, all aspects of RNA and mRNA lifecycle including splicing & transport, as well as DNA repair. Under normal conditions, FUS predominantly resides in the nucleus and shuttles between the nucleus and cytoplasm, maintaining cellular homeostasis*.

Under chronic stress or due to genetic mutations, this balance breaks down. FUS becomes mislocalized in the cytoplasm, forming aggregates and disrupting cellular pathways. If left untreated, mislocalized FUS disrupts mitochondria, creating a metabolic crisis, increasing neuronal stress, ultimately causing cell death.  In diseases like familial ALS, mutations in the FUS nuclear localization signal (NLS) impair nuclear import, while in sporadic ALS, FUS mislocalization occurs without mutations, driven by transcriptional and RNA export disturbances***.