Intercellular Adhesion Molecule 3: Structure, Cellular Functions, and Emerging Role in Human Diseases

The intercellular adhesion molecule 3 (ICAM3), also known as CD50, is a member of the intercellular adhesion molecule (ICAM) family. All ICAM proteins are type I transmembrane glycoproteins containing 2-9 immunoglobulin-like C2-type structural domains and bind to the lymphocyte function-associated antigen-1 (LFA-1) protein. ICAM3 is abundantly and constitutively expressed in all leukocytes and is probably the most important ligand for LFA-1 in initiating immune responses. In recent years, more and more studies have focused on ICAM3 and found that it is closely related to the pathogenesis of various diseases. Here, we summarize the genomic localization, protein structure, and basic functions of ICAM3, and discuss the research progress of ICAM3 in mediating immune cell function and other diseases. Further, we describe the regulatory role of ICAM3 on the progression of different types of malignant cancers and the associated signaling pathways. Our work assesses the feasibility of ICAM3 as a molecular marker for the diagnosis of human diseases and cancers, which may provide new targets for treating related diseases and cancers. As a typical transmembrane protein, we expect to find or synthesize specific small molecule inhibitors for the treatment of clinically relevant diseases.