Mutations in the tau gene cause familial frontotemporal dementia and parkinsonism linked to chromosome 17. Here we describe a novel missense mutation in exon 12 of the tau gene, G335V, in a German family with frontotemporal dementia of early age at onset, in the third decade of life. Functional analysis of recombinant tau protein with the G335V mutation showed a dramatically reduced ability to promote microtubule assembly and a more rapid and accelerated tau filament formation, suggesting that the primary effect of the mutation might be the provision of a pool of unbound tau making it available for aberrant tau aggregation.