MAPT encodes tau, a microtubule-associated protein that promotes microtubule assembly and stability while facilitating neuronal polarity establishment and maintenance 1. Tau functions as a linker protein, with its C-terminus binding axonal microtubules and N-terminus binding neural plasma membrane components 1. Short tau isoforms provide cytoskeletal plasticity, whereas longer isoforms preferentially stabilize microtubules; all six human tau isoforms are expressed in vivo 2. MAPT mutations cause frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), providing definitive evidence that pathological tau aggregation directly causes neurodegeneration 3. Pathogenic mutations promote tauopathy through diverse mechanisms, including altered tau aggregation propensity and prion-like propagation 34. Mutations such as P301S, V337M, and R406W induce tau filament formation with the Alzheimer fold structure, even in the absence of β-amyloid deposits 5. β-amyloid deposition accelerates pathological tau cell-to-cell propagation and intensifies tau accumulation 2. Beyond FTDP-17, tau pathology characterizes approximately 30 tauopathies, including Alzheimer's disease, Pick disease, and progressive supranuclear palsy 6. Understanding tau aggregation mechanisms and tau-induced neurodegeneration has critical implications for developing tau-targeting therapeutics 3.