Intercellular cell adhesion molecule-1 (CD54 or ICAM-1) is a cell surface glycoprotein that belongs to the immunoglobulin superfamily (IgSF) of adhesion molecules. CD54 is expressed at low levels in diverse cell types, and is induced by cytokines (TNF-?, interleukin-1) and bacterial lipopolysaccharide. Apical localization of CD54 on endothelial cells (or basolateral localization on epithelial cells) is a prerequisite for leukocyte trafficking through the endothelial (or epithelial) barrier. Apical expression of CD54 on epithelial cells mediates pathogen invasion as well as host defense, a pattern also observed in tumors. CD54 also functions as a co-stimulator on antigen presenting cells, binding to its receptor LFA-1 (leukocyte function-associated antigen-1) on the surface of T cells during antigen presentation. Cross-linking of CD54 or binding to its ligand triggers activation of Src family kinases and the Rho/ROCK pathway. Phosphorylation on Tyr485 of CD54 is required for its association with SHP-2. SHP-2 seems essential for CD54-induced Src activation.