Galectin-3 contains a carboxyl-terminal lectin domain and an amino-terminal non-lectin part consisting primarily of short tandem repeats. It is widely distributed in tissues and found in epithelial cells, fibroblasts, dendritic cells, and inflammatory cells. In many cell types studied, galectin-3 is present diffusely in the cytoplasm, but is also localized to the nucleus and subcellular structures, such as mitochondria, phagosomes and exosomes, under specific conditions. It is secreted by various cell types, including monocytes, macrophages, and epithelial cells, and the extracellular protein can bind to a large number of different glycoconjugates on the cell surfaces and extracellular matrices.

Galectin-3 can form dimers through intermolecular interactions that involve the N-terminal domain and can function bivalently. It thus has the potential to cross-link cell surface glycoproteins of various cells, causing cell activation (such as mediator release and superoxide production). It is also suited for mediating cell-cell and cell-extracellular matrix adhesion (including homotypic cell aggregation) by serving as a bridge to bind cells together or cells to extracellular matrix proteins. Moreover, it can induce migration of a number of different cell types, including monocytes, macrophages, and endothelial cells, possibly through binding to and activating a G-protein-coupled receptor(s). Galectin-3 is present on the cell surface. Cell surface galectin-3 on T cells can form multivalent complexes with N-glycans on TCR and thereby restrains the lateral mobility of TCR complexes and suppress TCR-mediated signal transduction.

Galectin-3 is also abundantly present inside the cells and has been shown to play important roles in some biological responses through its intracellular actions. It has been identified as a regulator of the cell cycle, apoptosis, and phagocytosis. The mechanisms underlying these functions have not been elucidated, but they probably involve the regulation of intracellular signaling pathways. Galectin-3 has in fact been shown to regulate such fundamental cellular processes as pre-mRNA splicing. It has also been shown to interact with an apoptosis regulator, Bcl-2, and stimulate the DNA-binding activity of a transcriptional factor, TTF-1.

Galectin-3 expression is dysregulated upon transformation of normal cells to tumor cells. It is highly expressed in hepatoma, subtypes of lymphomas, and thyroid carcinoma, although not expressed by the corresponding normal cells. Galectin-3 expression is upregulated in neoplasms induced by virus, ultraviolet light or chemicals. In mouse fibroblasts, galectin-3 expression is regulated in a manner comparable to other mitogen-activated genes, including the oncogenes c-fos and c-myc. Galectin-3 gene contains a responsive element to the tumor suppressor p53 and galectin-3 expression is down-regulated by p53. The known functions of galectin-3 suggest a role of this lectin in tumor cell invasion. It has been shown that the presence of galectin-3 in transformed cells can promote an invasive phenotype.

Galectin-3 is thus a pleiotropic regulator involved in a multitude of functions, both inside and outside the cell. While the extracellular functions are most likely due to this protein's binding to glycoconjugates, the intracellular functions probably does not involve lectin-carbohydrate interactions. Galectin-3's unusual proline-, glycine-, tyrosine-rich tandem repeats in the N-terminal region may contribute to galectin-3's multifunctionality, because these tandem repeats may be well suited for interactions with other intracellular components. Existing information suggests that galectin-3 may play an important role in a variety of physiological processes, including inflammation, neoplastic transformation, as well as innate and acquired immunity. Studies of galectin-3-deficient mice have provided evidence for a role of galectin-3 in the inflammatory response.