Fig. 7. Proposed model of SFPQ protein redistribution in ALS.

Under control conditions, the SFPQ gene expresses at least two splicing isoforms; wtSFPQ (red RNA) encodes a nuclear predominant protein, the other (altSFPQ; blue RNA) is largely degraded but encodes a primarily cytoplasmic protein. The altSFPQ protein exhibits reduced phase separation propensity and partially distinct protein interactome, including translation-associated machinery. In ALS models, wtSFPQ is reduced whereas altSFPQ is increased, possibly resulting in reduced nuclear and increased cytoplasmic SFPQ proteins, manifesting as the nuclear-to-cytoplasmic redistribution of total SFPQ protein in disease.