Fus, also known as Fused in Sarcoma, is an RNA-binding protein. It is involved in RNA metabolism and DNA repair processes, and its function is closely related to liquid-liquid phase separation (LLPS). It forms liquid compartments in cells, which is crucial for its physiological role [1,2]. Mutations in Fus are associated with neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) [3,4].

In Fus mutant mice generated to study ALS-FTD, a progressive, age-dependent motor neuron loss was observed due to a dose-dependent gain of toxic function. This was associated with the insolubility of Fus and related RNA-binding proteins. In this model, an antisense oligonucleotide (ION363) that silences Fus could delay motor neuron degeneration [6]. In FUS-ALS neurons derived from human induced pluripotent stem cells, the dynamics of stress granules (SGs) was disturbed, and heat-shock response (HSR) and integrated stress response (ISR) were upregulated [5].

In conclusion, Fus is essential for normal RNA metabolism and DNA repair, and its malfunction due to mutation is closely linked to neurodegenerative diseases. The use of mouse models, like the Fus mutant mice, has provided valuable insights into the role of Fus in ALS-FTD, highlighting its potential as a therapeutic target for these diseases.