The impact of acetylation at K294 on 4R tau aggregation can further be rationalized on the basis of the structure of tau fibrils purified from the 4R tauopathy Progressive Supranuclear Palsy (PSP; Fig. 6d): K294 forms a salt bridge with D314/S316 in the core of the tau PSP structure3,39. This evidence concerns the gene MAPT and progressive supranuclear palsy.