While the role of abnormal TDP-43 accumulation in both primary and secondary TDP-43 proteinopathies is not yet fully understood, the identification of TDP-43 mutations associated with ALS and FTD has provided clear evidence that altered TDP-43 processing can be a primary cause of neurodegeneration and is not just a secondary phenomenon [9], [10]. The gene discussed is TARDBP; the disease is frontotemporal dementia.