Collectively, our results (1) identify novel functions of RBM45; (2) define a new mechanism by which the stress-associated functions of RBPs contribute to their aggregation and inclusion formation; and (3) provide quantitative measures of the cell type and disease-specific patterns of RBM45 pathology that occur in ALS, FTLD, and AD. This evidence concerns the gene RBM45 and amyotrophic lateral sclerosis.