The Role of Galectin-3 in Liver Inflammation and Fibrosis

Galectin-3, a β-galactoside-binding lectin encoded by <i>LGALS3</i>, is increasingly recognized as a central mediator in liver disease and inflammation. Galectin-3 has the unique ability to cross-link glycosylated molecules, resulting in a broad range of functions, from receptor clustering to influence downstream signaling, to extracellular matrix stabilization and the regulation of cell adhesion. In the liver, it regulates fibrogenesis through hepatic stellate cell activation, oxidative stress regulation, apoptosis, and extracellular matrix deposition. Immunologically, galectin-3 contributes to leukocyte infiltration, macrophage polarization, inflammasome activation and T cell regulation. Elevated circulating and hepatic galectin-3 levels are reported across different stages of liver disease, including metabolic dysfunction-associated liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), metabolic dysfunction-associated steatohepatitis (MASH), and cirrhosis, correlating with disease stage and the risk of hepatocellular carcinoma. Translational studies highlight galectin-3 as both a biomarker and a therapeutic target. Clinical trials of galectin-3 inhibitors, including GB1211 (Selvigaltin) and GR-MD-02 (Belapectin), demonstrate safety and preliminary efficacy signals in reducing liver fibrosis, portal hypertension, and systemic inflammation. Preclinical models reinforce its role in modulating fibrogenic and inflammatory signaling, supporting drug development efforts. This review synthesizes current evidence on galectin-3 in liver disease and inflammation, with emphasis on mechanisms, biomarker potential, the requirements for clinical investigation and translational opportunities. By bridging molecular insights with ongoing therapeutic trials, galectin-3 appears to be an important driver of liver pathology and a promising target for liver-directed antifibrotic and anti-inflammatory therapies.