**1. Galectins**

Galectins are a class of carbohydrate binding proteins with high a ffinity to β-galactoside sugars that bind to them via their N- or- O-linked glycosylation [1,2]. They share primary structural homology in their carbohydrate-recognition domains (CRDs) included in a canonical sequence of ~130 amino acid backbone. They are synthesized as cytosolic proteins and reside in the cytosol or nucleus for much of their lifetime [3]. They form a β-sandwich [4,5] consisting of five or six anti-parallel β-sheet strands [6], forming a shallow groove for holding a disaccharide or oligosaccharide. Eight amino acids

form the CRD motif within this groove to mediate non-covalent binding. Additional amino acids enhance the specific interaction [5–9]. High affinity to the ABO blood groups is responsible for their hemagglutinin activity [10,11]. The galectins are classified into three categories [2]: (1) the prototype homo-dimers (gals 1, 2, 5, 7, 13–17, 19, 20), (2) the "tandem-repeat dimers" (gals 4, 6, 8, 9, 12) with short linkers, and (3) chimera-lectin (gal 3), with a C-terminal CRD and an N-terminal non-lectin for multimerization [12–15]. The multi-valent interaction facilitates crosslinking of signaling pathways, the formation of cell surface lattices, and endocytosis at the cell surface or in intracellular locations [16,17].

Today, we know of 20 members of the galectin family that interact with a plethora of molecules involved in inflammation, immune responses, cell trafficking, apoptosis, autophagy, trans-membrane signaling, and interactions with cytosolic and nuclear targets, nuclear transcription, gene expression, or mRNA splicing [18–21]. Galectins are able to translocate from intra- to extracellular compartments, and back. They affect signal transduction and apoptosis, growth, fibrosis, aggregation, adhesion, and cancer metastasis [22–27]. Hence, galectins are incorporated in the development of new therapeutics [22,27–29], and some are already in clinical development stages (https://galecto.com/ [30]).
