Abstract: Tau protein is encoded by the microtubule-associated protein tau (MAPT) gene and stabilizes microtubules in the neurons. Tau has unique biophysical properties that make it both highly water-soluble and positively charged. Although tau is an intrinsically disordered protein lacking defined secondary structures, it can acquire highly organized -sheet structures and stack into a filamentous inclusion such as a paired helical filament (PHF). This is a common feature of tauopathies including Alzheimer’s disease (AD). The progression of tauopathies, both biochemically and symptomatically, is directly correlated with the extent of tau fibrillization. Extensive research has been conducted to determine the mechanisms underlying this phenomenon. A growing body of research indicates that genetic mutations linked to autosomal dominant tauopathies may be insufficient to cause significant conformational changes in tau. Instead, several post-translational modifications, including phosphorylation, acetylation, ubiquitylation, and O-GlcNAcylation, as well as their complex interaction, appear to play a crucial role in inducing fibrillization (Park et al., 2018; Kim et al., 2021). Tau phosphorylation, which weakens the electrostatic interactions between tau and axonal microtubules, has been a primary pharmacological target for AD treatment (Basheer et al., 2023). It has, however, failed to provide significant benefits for patients.