Signal Transduct Target Ther. 2026 Jun 5;11(1):217. doi: 10.1038/s41392-026-02768-4.
ABSTRACT
Galectins are glycan-binding proteins that interact with diverse glycoconjugates and protein networks to regulate intracellular and extracellular signaling pathways governing fundamental biological processes. Increasing evidence implicates galectins in the pathogenesis of major human diseases, including cancer, cardiovascular disorders, neurodegeneration, metabolic disorders, and autoimmune conditions, in which they influence angiogenesis, metastasis, immune evasion, fibrosis, and cell fate decisions. Despite the structural similarities of galectins within their conserved carbohydrate recognition domains, individual galectin family members exhibit context-dependent functions and can even exert opposing effects across tissues and disease states, highlighting their complexity. The sixteen mammalian galectins are classified into prototypical, tandem-repeat, and chimeric subtypes, each characterized by distinct binding specificities and thus engaging in the regulation of unique signal transduction mechanisms. Here, we review current understanding of galectin structure, glycan recognition, and the signaling networks they orchestrate in human disease. We highlight their therapeutic potential as both biomarkers and drug targets, and critically evaluate ongoing clinical trials of galectin inhibitors, including modified carbohydrates, pectins, allosteric modulators, and monoclonal antibodies. Finally, we discuss how emerging technologies, such as single-cell glyco-RNA sequencing, CRISPR-based glycoengineering, and targeted protein degradation approaches, are advancing our understanding of galectin biology and accelerating the development of more effective galectin-directed therapeutics.
PMID:42248861 | DOI:10.1038/s41392-026-02768-4