TPPP (tubulin polymerization promoting protein) is a multifunctional regulator of microtubule dynamics with critical roles in both normal and pathological brain function. Physiologically, TPPP is expressed in oligodendrocytes where it promotes microtubule nucleation at Golgi outposts and stabilizes microtubule bundles, essential processes for myelin sheath elongation and formation of oligodendroglial projections 1. TPPP regulates microtubule dynamics by inhibiting HDAC6-mediated tubulin deacetylation, promoting tubulin acetylation and microtubule stabilization 23. Additionally, TPPP influences cell migration through ROCK1-mediated phosphorylation and cell proliferation through G1/S-phase regulation 34. Pathologically, TPPP exhibits "moonlighting" behavior—performing distinct disease-associated functions without genetic alteration 5. In synucleinopathies, TPPP interacts aberrantly with α-synuclein, promoting aggregation and inclusion formation characteristic of Parkinson's disease and multiple system atrophy (MSA) 65. In MSA, elevated SNCA and TPPP transcripts accumulate in glial cytoplasmic inclusions, with their co-enrichment contributing to pathogenesis 7. TPPP-α-synuclein hetero-association also inhibits autophagy-mediated protein degradation, exacerbating pathological accumulation 89. Conversely, TPPP loss correlates with poor hepatocellular carcinoma prognosis, indicating its tumor-suppressive functions 10.