This "double-edged sword" nature was powerfully illustrated by a landmark 2013 study, which first demonstrated that mutations within the PrLDs of hnRNPA1 and hnRNPA2B1 are a direct cause of multisystem proteinopathy (MSP) and amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD) 17. This evidence concerns the gene HNRNPA2B1 and amyotrophic lateral sclerosis.