The accumulation of aggregates of the microtubule-binding protein Tau represents a pathological hallmark in Alzheimer’s disease (AD). While Tau is primarily recognized for its interaction with microtubules, recent findings suggest the presence of Tau clusters near the plasma membrane, potentially serving as binding partners for Axonal Initial Segment (AIS)-related membrane proteins and synaptic proteins. Additionally, during AD, pathogenic tau is known to traverse the membrane via cell-to-cell transport. Furthermore, recently our group identified lipidation as a process enabling Tau’s interaction with the membrane. However, despite tau’s hydrophilic nature, the precise mechanism through which Tau dynamics might fulfill a novel physiological function by facilitating its interaction with hydrophobic lipid membranes remains elusive. In this study, we performed single-molecule imaging with total internal reflection fluorescence microscopy (TIRF) to observe tau dynamics near the plasma membrane of differentiated PC12 cells. Indeed, expression of Tau mutant constructs with inhibited lipidation in PC12 cells resulted in increased mobility of Tau near the plasma membrane. Moreover, treatment with an inhibitor targeting lipidation produced similar effects as observed with Tau mutants, suggesting that lipidation-mediated membrane interaction slows Tau mobility. In primary hippocampal neurons, we observed colocalization of Tau with lipidation-related proteins, and the Proximity Ligation Assay (PLA) confirmed their presence within 40nm proximity. This study introduces a novel post-translational modification mechanism enabling Tau interaction with the membrane. It show that Tau exhibits distinctive dynamic characteristics in close proximity to the plasma membrane, where its interaction with membrane-associated proteins could potentially serve as a potent mechanism for spatially guiding tau towards native membrane-mediated functions.