In this paper we refer to a couple of data reported previously458; in addition, new sets of experiments have also been performed that allowed us to suggest a plausible mechanism for the role of the unstructured N- and C-termini of TPPP/p25 in the dimer-derived MT bundling. Our previous electron microscopic studies underlined that the MTs are cross-linked by TPPP/p25, formed bundles of 25–26 nm in diameter consisting of dozens of MTs decorated by rows of tiny projections and dense particles with a periodicity of about 16 nm were observed211. In fact, the particles, likely dimers, express significant stabilization effect, similar to one as detected in the case of tau protein18. The tau protein, a key MAP of the brain MT system occurs in soluble form in normal neuronal cells, and the soluble tau-tau interactions display stabilizing effect as well on the MT structures1920. The formation of the pathological tau filaments has been reported, the development of which are promoted by the presence of MTs19. No TPPP/p25 filament formations have been detected as indicated in a recent paper as well to our knowledge; however, the formation of α-synuclein filaments has been established at substoichiometric TPPP/p25 concentration21.