Activated leukocyte cell adhesion molecule (ALCAM), designated as CD166, is a highly conserved 110 kDa transmembrane type-I glycoprotein that was first described as a CD6 ligand on leukocytes.? 583 amino acids ALCAM consists of a 27 amino acids signal peptide followed by a 500 amino acids extracellular domain, a 22 amino acids transmembrane domain, and a 34 amino acids cytoplasmic domain.? The amino acid sequence has shown to be homologous to neurolin, RAGE, and MUC18.?? ALCAM is expressed in a wide range of cells including neuronal, immune, epithelial, and stem cells of hematopoietic and mesenchymal origin. ALCAM mediates homotypic interactions as well as heterotypic interactions. ?ALCAM’s heterotypic interaction helps to mediate adhesion, migration, and tube formation in lymphatic endothelial cells.? It also supports dendritic cell adhesion to lymphatic endothelium, and plays important role in hematopoiesis and axon fasciculation. ?ALCAM is the only known ligand for CD6 and their interaction contributes to immunological synapse, T cell activation and proliferation.? ALCAM also promotes neurite extension, axon growth and axon guidance.? It mediates outgrowth and pathfinding for retinal ganglion cell axons.? ALCAM expression has been shown to correlate with enhanced melanoma invasion and metastasis, however anti-metastatic activity has also been reported in breast cancer.