Previous linkage and association studies have implicated a region at chromosome 9p21 as harboring a shared susceptibility locus for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Now, parallel studies by Bryan Traynor and colleagues (Neuron, published online 21 September 2011; doi:10.1016/j.neuron.2011.09.010) and Rosa Rademakers, Ian Mackenzie and colleagues (Neuron, published online 21 September 2011; doi:10.1016/j.neuron.2011.09.011) have identified a hexanucleotide-repeat expansion in a previously uncharacterized gene in the 9p21 region as a major contributor to the familial and sporadic forms of these diseases. Both groups discovered the expansion through sequencing and showed that it segregated with disease in large families with confirmed linkage to the 9p21 region. They subsequently extended their analyses to familial and sporadic forms of ALS and FTD and found that the expansion was strongly associated with both diseases in multiple case-control collections. In the study by Traynor and colleagues, the expansion was found in 46% of familial ALS and 21% of sporadic ALS cases in the Finnish population compared to less than 1% of controls. The repeat is located in C9orf72, a gene of unknown function expressed broadly in spinal cord and brain tissues, and may contribute to disease risk by promoting the formation of nuclear RNA foci.