TDP-43 is of fundamental importance to ALS/FTD, not only because >95% of ALS and around 50% of FTD patients present with TDP-43 proteinopathy (Arai et al., 2006; Mackenzie et al., 2007; Neumann et al., 2006), but also because familial ALS and FTD cases can harbour TARDBP mutations. The gene discussed is TARDBP; the disease is frontotemporal dementia.