In particular, we summarize in vitro and in vivo evidence of EV-mediated prion-like misfolded protein propagation in ALS, focusing on the proteins encoded by the main ALS-causative genes, i.e. superoxide dismutase 1 (SOD1), TARDBP, Fused-in-sarcoma (FUS) and Chromosome 9 open reading frame 72 (C9orf72). Then, since alteration of RNA homeostasis is a crucial process in ALS, we provide an overview on EV-mediated non-coding RNA transmission and we point out the contribution of miRNAs into the regulation of gene expression in ALS. Here, TARDBP is linked to amyotrophic lateral sclerosis.