Cell adhesion is of utmost importance in normal development and cellular functions. ICAM-5 (intercellular adhesion molecule-5, telencephalin, TLN) is a member of the ICAM family of adhesion proteins. As a novel cell adhesion molecule, ICAM-5 shares many structural similarities with the other members of IgSF, especially the ICAM subgroup; however, ICAM-5 has several unique properties compared to the other ICAMs. With its nine extracellular Ig domains, ICAM-5 is the largest member of ICAM subgroup identified so far. Therefore, it is much more complex than the other ICAMs. The expression of ICAM-5 is confined to the telencephalic neurons of the central nervous system whereas all the other ICAM members are expressed mostly by cells in the immune and blood systems. The developmental appearance of ICAM-5 parallels the time of dendritic elongation and branching, and synapse formation in the telencephalon. As a somatodendrite-specific adhesion molecule, ICAM-5 not only participates in immune-nervous system interactions, it could also participate in neuronal activity, Dendrites’ targeting signals, and cognition. It would not be surprising if future investigations reveal more binding partners and other related functions of ICAM-5. 1. Introduction The immunoglobulin superfamily (IgSF) comprises over 100 members are in vertebrates and most of its members expressed at the cell surface. Molecules carrying immunoglobulin (Ig) domains are endowed with broad functions which include cytoskeletal organization, endocytosis, adhesion, migration, growth control, immune recognition, viral attachment, and tumor progression. The ever growing number of newly discovered Ig molecules has made this superfamily increasingly complex. Intercellular adhesion molecules (ICAMs) are a subset of the IgSF that bind to leukocyte β2 integrins. There are now five members of this family: ICAM-1 has a relatively broad distribution in different tissues, whereas ICAM-2, -3, -4, and -5 show more restricted patterns of tissue expression. The five ICAMs share many structural and functional features [1]. A 26？kb region on human 19p13.2 contains ICAM-1 (MIM 147840), ICAM-4, and ICAM-5 (MIM 601852) genes [2]. Structurally, all ICAMs have lg-like domains; functionally, most ICAMs participate in immune system interaction. Notably, ICAM-5/TLN may play important roles both in the immune and nervous systems. In this review, the main focus is placed on the structure, expression, and function analysis of mouse, rabbit, and human ICAM-5. Here I will discuss the characterizations of ICAM-5 gene and protein
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