Galectin-8 (Gal-8)

Galectin-8 is a **tandem-repeat type β-galactoside-binding lectin** encoded by the *LGALS8* gene in humans[5][1]. It contains two distinct carbohydrate recognition domains (CRDs)—N-terminal (Gal-8N) and C-terminal (Gal-8C)—joined by a flexible linker; each domain has distinct glycan binding specificity[1][2][6][8]. The protein modulates **cell adhesion**, acts as a **matricellular protein** potent as fibronectin, and regulates cellular and matrix interactions primarily through binding to glycans and integrins, thereby activating intracellular signaling cascades[3]. Galectin-8 is also involved in **autophagy**, notably sensing lysosomal or vacuolar damage and signaling to mTOR, which induces autophagic or metabolic changes[5][7]. It acts as an intracellular danger recognition receptor by labeling damaged vacuoles and recruiting autophagic machinery, providing defense against intracellular pathogens[5]. The protein plays complex roles in **cancer biology**, with evidence for both tumor-promoting and suppressive actions[5][9]. Recent work links it to the modulation of **osteoclast function** and bone resorption, especially through regulation of mTORC1 and cell adhesion proteins[7]. Multiple isoforms exist due to alternative splicing, differing mainly in linker region length, which may confer distinct biological properties[7]. No approved drugs directly target Galectin-8, but several research ligands, such as synthetic carbohydrate mimetics, show selectivity for its domains[9]. Safety considerations in therapeutic targeting include potential unwanted effects on immunity, cell adhesion, and tissue homeostasis due to Galectin-8’s diverse physiological roles[3][5].

Other names

LGALS8Gal-8Galectin 8

Ligands and inhibitors typically block or mimic the carbohydrate recognition domains, altering Galectin-8 interactions with cell surface or extracellular matrix glycoconjugates, thus modulating downstream processes such as immune signaling, cell adhesion, or autophagy[1][9].