The study identifies tubacin, a small-molecule inhibitor of α-tubulin deacetylation, which selectively targets class II histone deacetylase 6 (HDAC6). Tubacin increases α-tubulin acetylation without affecting histone acetylation, gene expression, or cell-cycle progression. It does not stabilize microtubules but inhibits cell motility and disrupts the localization of p58, a Golgi membrane-associated protein. The results suggest that selective inhibition of HDAC6-mediated α-tubulin deacetylation could have therapeutic applications as antimetastatic and antiangiogenic agents.The study identifies tubacin, a small-molecule inhibitor of α-tubulin deacetylation, which selectively targets class II histone deacetylase 6 (HDAC6). Tubacin increases α-tubulin acetylation without affecting histone acetylation, gene expression, or cell-cycle progression. It does not stabilize microtubules but inhibits cell motility and disrupts the localization of p58, a Golgi membrane-associated protein. The results suggest that selective inhibition of HDAC6-mediated α-tubulin deacetylation could have therapeutic applications as antimetastatic and antiangiogenic agents.