Cell adhesion is of utmost importance for normal development and cellular functions. ICAM-5 (intercellular adhesion molecule-5, telencephalin) is a member of the ICAM-family of adhesion proteins. These proteins bind to leukocyte beta(2)-integrins (CD11/CD18), but ICAM-5 is exceptional in several ways. It is solely expressed in the mammalian forebrain, appears at the time of birth, and is located in the soma and dendrites of neurons. It is structurally more complex than the others, and also shows homophilic adhesion. Recent studies show that it is important for the regulation of immunological activity in the brain and for the development of neuronal synapses and signal transmission.