In 2011, a hexanucleotide-repeat-expansion mutation in the first intron of the C9orf72 gene was reported to be the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).  How this mutation leads to pathogenicity is currently unclear. There is compelling evidence that this repeat expansion mutation confers the transcription and translation of the intron 1 in both sense and antisense directions, and each in 3 reading frames, through a poorly understood mechanism called Repeat-Associated Non-ATG (RAN) translation. The resultant 6 junk polydipeptides translated from the hexanucleotide repeat sequence accumulate in the brain of ALS patients and have been postulated to be toxic to the neurons. We present our strategy and work-in-progress results towards unravelling the pathomechanisms of these junk proteins in C9orf72-ALS and FTD disorders employing the unique toolsets our lab has in studying the impact of protein aggregation on cell health. Several of the dipeptide repeats were found to be potently toxic to the NSC-34 motor neuron cell line and also seemed to enrich in the nucleus and alter the DNA morphology.  In addition, we have characterized the oligomeric state of these proteins using analytical ultracentrifugation of recombinant proteins expressed in mammalian cell lysates; it appears that there is no evidence that they consistently form large aggregates but rather form more soluble monomers and oligomers.  Ultimately this is a work in progress, but our efforts will contribute new insight project may help define new therapeutic targets for not only the incurable ALS and FTD diseases but also the other repeat expansion diseases.