Human HDAC6 (1215 a.a. residues) possesses two separate putative catalytic domains, both of which are fully functional and contribute independently to the overall activity of HDAC6. 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. HDAC6 may participate in coordinating expression of a group of genes involved in the remoldeling of chromatin during cell differentiation.