A mutation leading to an excessive number of hexanucleotide repeats (HREs) within the first intron of C9ORF72 creates dipeptide repeat peptides PR_N, including PR20. PR20 is highly toxic to cells in vitro and vivo. The significant mutation of C9ORF72 leading to PR20 formation is linked to the pathology of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, the exact mechanisms that cause the pathology remain unclear. Therefore, there is ongoing research to understand the underlying mechanism of PR20 toxicity and find therapies for these conditions.

PR20 has been extensively studied in numerous cell lines, including neuronal cells. It has been successfully used with fluorescent tags to investigate its localisation, including HA and GFP. PR20 can penetrate the cell, aggregate in the nucleoli, and lead to cell death. There are also observations about the inherent disordered nature of PR20 affecting translation in the nucleus and expression, causing nuclear stress. The use of PR20 on cells has allowed large-scale screening for inhibitors of PR20 activity; this highlighted BET Bromodomain inhibitors were effective at protecting the cell from PR20 by inhibiting nuclear stress. Further work with PR20 could help clarify the mechanism of toxicity and improve the treatments for ALS and FTD.