Galectin 3

Overview

Galectin 3 is a member of the galectin family of β-galactoside-binding proteins and is encoded by LGALS3. It is a multifunctional protein implicated in cell–cell and cell–matrix interactions, immune regulation, inflammation, fibrosis, and tumor biology. In biomedical research, galectin 3 is often discussed as both a circulating biomarker and a mechanistic mediator of disease processes, particularly in settings involving tissue injury, chronic inflammation, metabolic dysfunction, and cancer.

Functionally, galectin 3 has been associated with pathways relevant to metabolic dysfunction–associated steatotic liver disease, Metabolic dysfunction associated steatohepatitis (MASH), cardiovascular injury, and neuroinflammation. It is also studied as a therapeutic target in oncology, where galectin-1 and galectin-3 are sometimes considered together because of their overlapping roles in tumor progression, immune evasion, and the hallmarks of cancer. Recent studies have also linked galectin 3 to disease contexts involving obesity, proinflammatory cytokine signaling, TGF-β1 and VEGF-related fibrotic or angiocrine pathways, Parkinson's disease, and a range of solid tumors.

Focus of Latest Publications

Recent publications have examined Galectin-3 (Gal-3) as a therapeutic target in cancer, inflammatory disease, and systemic toxicity, with several studies focusing on its immunomodulatory and pro-tumor roles. In aggressive meningioma, Gal-3 was reported to be more highly expressed in atypical and anaplastic subtypes than in normal brain tissue, and preclinical work tested the Gal-3 inhibitor TD139 in combination with direct current stimulation approaches. In a human co-culture model, low-intensity direct current electrostimulation altered HLA class I and II expression, while Gal-3 was found to activate microglia and promote CD4(+) T-cell differentiation toward Th2 and Treg phenotypes. Sequential treatment with immunomodulatory direct current electrostimulation followed by TD139 induced anaplastic meningioma cell death without affecting neurons, and in an orthotopic allograft model, TD139 plus transcranial direct current stimulation significantly reduced tumor growth and improved survival relative to controls or either treatment alone.

Gal-3 also emerged in studies of metabolic and inflammatory disease. In a mouse and human analysis of metabolic dysfunction-associated steatohepatitis with sarcopenia, LGALS3 was identified among MASH-induced hepatokines elevated in circulation in both animal models and sarcopenic patients with advanced chronic liver disease. Recombinant LGALS3, like Lipocalin 2, induced atrophy in C2C12 myotubes, altered mitochondrial metabolism, and impaired function in human 3D skeletal muscle organoids, supporting a role for Gal-3-associated hepatokine signaling in muscle wasting. In a separate rat model of cisplatin-induced splenic toxicity, modified citrus pectin, which modulates Gal-3, reduced Gal-3 levels in the spleen and altered immune cell distribution, including a marked reduction in CD3(+) T-cell immunoreactivity, although it did not restore splenic architecture.

Additional studies linked Gal-3 to biomarker and inhibitor development. In plasma small-extracellular vesicles from obese, chemotherapy-naïve breast cancer patients, Gal-3 was part of a network associated with fibronectin 1, von Willebrand factor, and syndecan-2; Gal-3 was reduced in small-EVs but elevated in breast carcinoma tissues and microvesicle-enriched EVs. In Parkinson's disease substantia nigra pars compacta tissue, proteomic analysis identified increased LGALS3 among markers of neuroinflammation and mitochondrial impairment across Braak stages. Finally, medicinal chemistry work produced an orally available halothiazole glycomimetic, GB1841, as a dual galectin-1/galectin-3 inhibitor; both selective and dual inhibition reduced LL/2 lung cancer growth in a syngeneic mouse model, supporting further development of Gal-3-targeted therapy.

Key Publications

NEWJun Effects of Galectin-3 inhibitors paired with direct current stimulation in preclinical models of aggressive meningioma. (Molecular biology reports, 2026, PMID 42363999): "Galectin-3 (Gal-3), a multifunctional β-galactoside-binding lectin, is more highly expressed in atypical and anaplastic meningioma subtypes than in normal brain tissue."
NEWJun Hepatokines lipocalin 2 and osteopontin drive muscle atrophy in MASH. (Molecular metabolism, 2026, PMID 42270040): "we identified three MASH-induced hepatokines, namely LCN2, LGALS3 and OPN."
May Molecular Insights into Parkinson's Disease Progression: A Multi-omics Analysis of the Substantia Nigra Pars Compacta across Braak Stages. (Experimental neurobiology, 2026, PMID 42130054): "Proteomic analyses further highlighted increased levels of neuroinflammation and mitochondrial impairment markers, including SNCA, GPNMB, and LGALS3, some of which may serve as biomarkers of disease severity."
May Modified citrus pectin modulates splenic immune responses and galectin expression following cisplatin treatment in Wistar rats. (Journal of molecular histology, 2026, PMID 42126478): "Modified citrus pectin (MCP), a polysaccharide from citrus fruits, modulates galectin-3 (Gal-3) and immune responses."
May Plasma small-extracellular vesicles' proteomic signature in neoadjuvant chemotherapy-naïve breast cancer patients. (PloS one, 2026, PMID 42085441): "Bioinformatics and STRING networks revealed interactions with Syndecan-2 (SDC2) and Galectin-3 (Gal-3)."
May An Orally Available Halothiazole Glycomimetic as a Cancer-Targeting Dual Galectin-1 and Galectin-3 Inhibitor. (Journal of medicinal chemistry, 2026, PMID 42052938): "Galectin-1 and galectin-3 have been proposed to together be involved in all 10 hallmarks, suggesting that development of a combined galectin-1/3 inhibitor would be beneficial."