WNT2 is a secreted glycoprotein ligand that functions in the canonical Wnt signaling pathway by binding to frizzled family receptors and activating transcription factors of the TCF/LEF family. In hepatic physiology, WNT2 is secreted by liver sinusoidal endothelial cells and controls cholesterol uptake and bile acid conjugation in hepatocytes through receptor FZD5 1. WNT2 plays critical roles in liver zonation and regeneration, with endothelial cell-derived WNT2 maintaining metabolic zonation by activating β-catenin targets in zone 3 hepatocytes 2. Beyond the liver, WNT2 contributes to cardiac fibrosis following myocardial infarction by activating β-catenin/NF-κB signaling through cooperation of Fzd4 and LRP6 receptors 3. In pathological conditions, WNT2 promotes skin fibrosis through a mechanosensitive Piezo1-Wnt2-CCL24 positive feedback loop 4. WNT2 expression is upregulated in gastrointestinal cancers, particularly gastric and colorectal cancers, where it may serve as a tumor marker 5. The protein also facilitates hepatocyte-sinusoid crosstalk in liver organoids, promoting hepatocyte differentiation and endothelial network formation 6. Therapeutically, WNT2 shows promise for treating acute liver failure and drug-induced liver injury through promotion of hepatocyte regeneration 7.