Major regulator of extracellular matrix organization during tissue remodeling (By similarity). Catalyzes the transfer of a heavy chain (HC) from inter-alpha-inhibitor (I-alpha-I) complex to hyaluronan. Cleaves the ester bond between the C-terminus of the HC and GalNAc residue of the chondroitin sulfate chain in I-alpha-I complex followed by transesterification of the HC to hyaluronan. In the process, potentiates the antiprotease function of I-alpha-I complex through release of free bikunin (By similarity). Acts as a catalyst in the formation of hyaluronan-HC oligomers and hyaluronan-rich matrix surrounding the cumulus cell-oocyte complex, a necessary step for oocyte fertilization (PubMed:12668637). Assembles hyaluronan in pericellular matrices that serve as platforms for receptor clustering and signaling. Enables binding of hyaluronan deposited on the surface of macrophages to LYVE1 on lymphatic endothelium and facilitates macrophage extravasation. Alters hyaluronan binding to functionally latent CD44 on vascular endothelium, switching CD44 into an active state that supports leukocyte rolling (By similarity). Modulates the interaction of chemokines with extracellular matrix components and proteoglycans on endothelial cell surface, likely preventing chemokine gradient formation. In a negative feedback mechanism, may limit excessive neutrophil recruitment at inflammatory sites by antagonizing the association of CXCL8 with glycosaminoglycans on vascular endothelium (By similarity). Has a role in osteogenesis and bone remodeling. Inhibits BMP2-dependent differentiation of mesenchymal stem cell to osteoblasts. Protects against bone erosion during inflammation by inhibiting TNFSF11/RANKL-dependent osteoclast activation (PubMed:18586671) (By similarity). Interacts (via Link domain) with inter-alpha-inhibitor (I-alpha-I) component bikunin. Interacts with ITIH2/HC2; this interaction is required for transesterification of the HC to hyaluronan. Interacts (via Link and CUB domains) with ITIH1. Chondroitin sulfate may be required for the stability of the complex. Interacts (via Link domain) with various C-X-C and C-C chemokines including PF4, CXCL8, CXCL11, CXCL12, CCL2, CCL7, CCL19, CCL21, and CCL27; this interaction interferes with chemokine binding to glycosaminoglycans. Interacts (primarily via Link domain) with BMP2; this interaction is inhibited by hyaluronan. Interacts (via both Link and CUB domains) with TNFSF11. Interacts (via CUB domain) with FN1 (via type III repeats 9-14); this interaction enhances fibronectin fibril assembly. TNFAIP6 may act as a bridging molecule between FN1 and THBS1. Expressed in epiphyseal and metaphyseal bone marrow of both the femur and tibia (at protein level). Expressed in cumulus cell-oocyte complexes during expansion. The Link domain interacts with various extracellular matrix components, including heparin, heparan sulfates, hyaluronan and I-alpha-I complex. It is required for binding to various chemokines. The CUB domain is necessary for calcium ion binding and transesterification reaction. It is required for binding to FN1. Mutant female mice are infertile due to impaired cumulus oophorus expansion upon gonadotropin surge (PubMed:12668637). Mutant mice have twice the bone mass of wild-type littermates. They show increased trabecular number and trabecular thickness (PubMed:18586671).