α-Tubulin acetylation at lysine 40 (α-tubulin K40ac) is a post-translational modification that marks long-lived microtubules and plays a role in various cellular functions. This acetylation is associated with the stabilization of microtubules, particularly in structures like axons and cilia. It is believed to influence microtubule dynamics, potentially by affecting lateral interactions among protofilaments and increasing microtubule stability. α-Tubulin K40 acetylation is also implicated in intracellular transport, cell division, and cell migration, as well as in neuronal development, including axonal transport, neuronal migration, and axonal growth. Furthermore, it has been suggested that acetylated microtubules facilitate the transport of the Hippo regulator Merlin, which is crucial for contact inhibition of proliferation and cell-substrate adhesion. The modification is regulated by the acetyltransferase αTAT1 and deacetylases like HDAC6 and SIRT2, and it serves as a stable microtubule marker, enhancing the binding of motor proteins and playing a role in early polarization events in neurons. Deficiency in α-tubulin acetylation has been linked to impaired axonal transport and neurodegenerative disorders. Thus, α-tubulin (acetyl K40) is critical for maintaining the structural integrity of microtubules and regulating key cellular processes.