Different large-scale approaches in yeast and other cell paradigms (Drosophila and human cells) supported the linkage between ALS/FTD and the function of intra- and extra-nuclear membrane-less organelles, identifying some nucleolar proteins, cytosolic stress granules components and nucleocytoplasmic trafficking factors as genetic modifiers (i.e., suppressors or enhancers) of the cytotoxicity triggered by ALS-related proteins, such as C9orf72 DPRs (Jovičič et al., 2015; Lee et al., 2016). This evidence concerns the gene C9orf72 and amyotrophic lateral sclerosis.