HAS2 (hyaluronan synthase 2) catalyzes the addition of GlcNAc or GlcUA monosaccharides to synthesize hyaluronan (HA), a major extracellular matrix component essential for tissue architecture, cell adhesion, migration, and differentiation 12. As one of three hyaluronan-synthesizing isoenzymes, HAS2 is particularly responsible for high molecular mass HA synthesis. HAS2 expression is regulated by multiple pathways: PDGF-BB stimulation upregulates HAS2 via ATF6 transcriptional activation in orbital fibroblasts 3, while METTL3-mediated m6A modification destabilizes HAS2 mRNA 3. ZEB1, an EMT-inducing transcription factor, upregulates HAS2 alongside ITIH2 to remodel the HA network and enhance cancer cell motility and invasion 4. In disease contexts, elevated HAS2 expression promotes malignancy across multiple cancers. Myofibroblastic cancer-associated fibroblasts express HAS2 to promote intrahepatic cholangiocarcinoma progression 5. HAS2 overexpression drives inflammatory responses and abnormal folliculogenesis in polycystic ovary syndrome, which can be reversed by berberine-mediated HAS2 downregulation 6. In colorectal cancer liver metastasis within steatotic liver, HAS2-derived HA activates YAP in cancer cells, creating a bidirectional CAF-tumor feedback loop that suppresses anti-tumor immunity 7. Clinically, HAS2 represents a targetable therapeutic pathway in cancer and inflammatory diseases.