A working model of RNA-induced protein aggregation and neurodegeneration. We propose that RNA sequence in the 3′UTR of NF-L mRNA or cognate binding factors confer enhanced reactivity (*) to translated NF-L protein and that enhanced reactivity promotes NF assembly or aggregation of NF-L protein. The latter phenomenon could promote aggregation of mutant SOD1 proteins or other proteins with neurotoxic effects on neurons-at-risk in neurodegenerative diseases.