{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n FUS is an RNA‐binding protein with multifaceted functions in the regulation of gene expression, RNA processing, and the DNA damage response. Under physiological conditions, FUS predominantly resides in the nucleus where it is implicated in transcriptional regulation, pre‐mRNA splicing, RNA transport, and the formation of dynamic ribonucleoprotein granules. Central to these roles is its intrinsically disordered, low‐complexity domain, which enables liquid–liquid phase separation to form transient, liquid‐like assemblies that facilitate efficient RNA metabolism and DNA repair."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In normal cells, nuclear import of FUS is mediated by binding to Transportin through a non‐classical nuclear localization signal, ensuring that FUS remains predominantly nuclear. However, mutations, particularly those affecting the C‐terminal nuclear localization signal, disrupt this import mechanism, resulting in pathological mislocalization to the cytoplasm. Cytoplasmic accumulation promotes aberrant phase transitions under stress conditions, leading to its incorporation into stress granules and the formation of insoluble, fibrillar aggregates, which are strongly associated with neurodegenerative disorders such as amyotrophic lateral sclerosis and frontotemporal dementia."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, post‐translational modifications—such as arginine methylation—regulate FUS’s propensity to phase separate, whereas disease‐associated mutations further perturb its dynamic behavior by enhancing its aggregation into cytoplasmic inclusions. These alterations impair normal RNA and protein homeostasis by disrupting both the reversible assembly of functional ribonucleoprotein granules and normal nuclear functions, thereby contributing to neurodegeneration."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "T J Kwiatkowski, D A Bosco, A L Leclerc, et al. 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