– Siglec-8 is also known as SIGLEC8, SAF2, SIGLEC-8, SIGLEC8L and sialic acid binding Ig like lectin 8, is an approximately 75 kDa transmembrane glycoprotein in the Siglec family of sialic acid-binding immune regulatory molecules. Siglec-8 is expressed on eosinophils, basophils, and mast cells, and it shows a binding preference for the carbohydrate 6-O sulfated sLex. At the tissue level, Siglec-8 mRNA was found to be most highly expressed in lung, PBMCs, spleen, and kidney. Mature human Siglec-8 consists of a 347 amino acid (aa) extracellular domain (ECD) with three Ig-like domains, a 21 aa transmembrane segment, and a 115 aa cytoplasmic domain with two tyrosine based signaling motifs. Alternative splicing generates additional isoforms that either lack most of the second Ig-like domain or have a substituted cytoplasmic domain without the signaling motifs. Cross-linking of Siglec-8 inhibits Fc epsilon RI alpha induced mast cell degranulation. It also induces eosinophil apoptosis, an effect which is enhanced by the eosinophil-activating cytokines IL-5, IL-33, and GM-CSF.