HDAC6 is a member of the class II mammalian histone deacetylases. Human HDAC6 is composed of 1215 amino acid residues. It possesses two separate putative catalytic domains. Both catalytic domains are fully functional HDACs and contribute independently to the overall activity of HDAC6 protein. A very potent NES is present at the amino-terminus of HDAC6, which was found to play an important role in regulating the shuttling of HDAC6 protein between cytoplasm and nucleus. The shuttling process may be a critical regulatory mechanism of HDAC6 function.