Hyaluronan (HA) is a major component of the extracellular matrix (ECM) and plays a critical role in immune regulation and tissue injury. HA is synthesized by three types of hyaluronan synthases (HAS1, HAS2, and HAS3) and degraded by hyaluronidases. HA fragments can stimulate inflammatory responses by interacting with Toll-like receptors (TLR4 and TLR2) and CD44. HA also protects epithelial cells by interacting with TLR2 and TLR4. HA regulates inflammation, tissue injury, and repair by modulating inflammatory cell recruitment, cytokine release, and stem cell migration. HA is involved in various physiological and pathological processes, including wound healing, tissue repair, and immune responses. HAS1, HAS2, and HAS3 have distinct roles in HA synthesis and regulation. HAS1 is involved in wound healing and inflammation, while HAS2 is important for cardiac development and limb formation. HAS3 is involved in keratinocyte migration and wound healing. HA degradation is mediated by hyaluronidases, which can be inhibited by various compounds. HA fragments can induce inflammatory responses and affect immune cell function. HA-binding proteins such as CD44, RHAMM, TSG-6, Brevican, Neurocan, and HABP1 play important roles in HA interactions and tissue repair. These proteins are involved in various biological processes, including cell adhesion, migration, and inflammation. HA and its binding proteins are essential for maintaining tissue homeostasis and regulating immune responses in human diseases.Hyaluronan (HA) is a major component of the extracellular matrix (ECM) and plays a critical role in immune regulation and tissue injury. HA is synthesized by three types of hyaluronan synthases (HAS1, HAS2, and HAS3) and degraded by hyaluronidases. HA fragments can stimulate inflammatory responses by interacting with Toll-like receptors (TLR4 and TLR2) and CD44. HA also protects epithelial cells by interacting with TLR2 and TLR4. HA regulates inflammation, tissue injury, and repair by modulating inflammatory cell recruitment, cytokine release, and stem cell migration. HA is involved in various physiological and pathological processes, including wound healing, tissue repair, and immune responses. HAS1, HAS2, and HAS3 have distinct roles in HA synthesis and regulation. HAS1 is involved in wound healing and inflammation, while HAS2 is important for cardiac development and limb formation. HAS3 is involved in keratinocyte migration and wound healing. HA degradation is mediated by hyaluronidases, which can be inhibited by various compounds. HA fragments can induce inflammatory responses and affect immune cell function. HA-binding proteins such as CD44, RHAMM, TSG-6, Brevican, Neurocan, and HABP1 play important roles in HA interactions and tissue repair. These proteins are involved in various biological processes, including cell adhesion, migration, and inflammation. HA and its binding proteins are essential for maintaining tissue homeostasis and regulating immune responses in human diseases.