The neural cell adhesion molecule (NCAM) is a membrane-bound glycoprotein involved in homophilic interactions that facilitate cell-cell adhesion. In addition to a number of membrane-bound isoforms, NCAM also exists in several soluble isoforms that have been identified in cerebrospinal fluid, blood serum, brain tissue, and cell culture media. Soluble NCAM can be produced in a number of ways, such as alternative splicing of the transcript from NCAM1 and enzymatic processing of the extracellular domain at the cell membrane. Soluble NCAM interferes with homophilic NCAM interactions mediated by membrane-bound NCAM, thereby reducing NCAM-dependent adhesion, and can modulate neurite outgrowth in vitro-a property that likely is dose-dependent. The biological effects of overexpressing soluble NCAM in transgenic animals include a perturbation of synaptic connectivity and the development of abnormal behaviors. Similarly, the levels of soluble NCAM in cerebrospinal fluid and blood serum are altered in many human neurological disorders.