WNT2B encodes a secreted signaling molecule that functions as a ligand for frizzled receptors and plays critical roles in canonical Wnt/β-catenin signaling across multiple organ systems. In kidney injury, WNT2B expression by SOX9-positive epithelial cells drives fibroblast proliferation and progression from acute kidney injury to chr1 kidney disease 1. The protein promotes tumor-associated macrophage polarization through Wnt2b/β-catenin/c-Myc signaling, enhancing hepatocellular carcinoma progression via epithelial-mesenchymal transformation 2. WNT2B serves as an immunosuppressive factor in cancer, with its reduction enhancing dendritic cell function and CD8+ T-cell responses 3. In intestinal development, mesenchymal WNT2B is essential for human intestinal epithelial function and stem cell maintenance, with mutations causing Diarrhea-9 syndrome characterized by severe congenital diarrhea 4. The protein also regulates aldosterone production in the adrenal zona glomerulosa through non-canonical Wnt signaling, with loss-of-function mutations causing familial hyperreninemic hypoaldosteronism 5. Additionally, WNT2B promotes angiogenesis in ectopic pregnancies 6 and drives inflammatory bowel disease fibrosis by activating NK cells to secrete IL-33 7. These findings establish WNT2B as a multifunctional regulator of tissue homeostasis, fibrosis, and disease pathogenesis.