HPOB is a potent inhibitor of histone deacetylase 6 (HDAC6; IC50 = 56 nM). It is at least 30-fold less effective against other HDACs. Through its effects on HDAC6, HPOB induces acetylation of α-tubulin but not histones. HPOB reduces the growth, but not the viability, of normal and transformed cells. It enhances the death of transformed cells as triggered by the topoisomerase II inhibitors etoposide and doxorubicin. HPOB enhances the cytotoxicity of the broad spectrum HDAC inhibitor SAHA against cancer cells in nude mice carrying an androgen-dependent CWR22 human prostate cancer xenograft.