Cryoelectron microscopy has recently revealed that tau fibrils adopt distinct conformations in particular diseases, potentially linking these conformations with disease-specific pathophysiology.1 Rare mutations in the MAPT gene that encodes tau can cause dominantly inherited frontotemporal dementias with tau pathology.2 This provides strong evidence that the aggregation of tau can drive disease progression in rare tauopathies and potentially also in more common sporadic tauopathies. The gene discussed is MAPT; the disease is frontotemporal dementia.