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The FEBS journal 290(3), 821 - 836 (2022). doi:10.1111/febs.16616, Human histone deacetylase 6 (HDAC6) is a structurally unique, multido-main protein implicated in a variety of physiological processes includingcytoskeletal remodelling and the maintenance of cellular homeostasis. Ourcurrent understanding of the HDAC6 structure is limited to isolateddomains, and a holistic picture of the full-length protein structure, includ-ing possible domain interactions, is missing. Here, we used an integrativestructural biology approach to build a solution model of HDAC6 by com-bining experimental data from several orthogonal biophysical techniquescomplemented by molecular modelling. We show that HDAC6 is bestdescribed as a mosaic of folded and intrinsically disordered domains thatin-solution adopts an ensemble of conformations without any stable inter-actions between structured domains. Furthermore, HDAC6 forms dimers/higher oligomers in a concentration-dependent manner, and its oligomer-ization is mediated via the positively charged N-terminal microtubule-binding domain. Our findings provide the first insights into the structure offull-length human HDAC6 and can be used as a basis for further researchinto structure function and physiological studies of this unique deacetylase., Published by Wiley-Blackwell, Oxford [u.a.]