Ig (immunoglobulin) superfamily members exhibit functional characteristics including immune responses, growth factor signaling and cell adhesion. IGSF4D (Ig superfamily member 4D) is also known as CADM2 (cell adhesion molecule 2), Necl-3 (nectin-like protein 3) or synCAM2 and is a 435 amino acid protein that is a member of the nectin family. IGSF4D contains two C2-type domains and one V-type domain, which are characteristic of the nectin family and are thought to function in molecular recognition. IGSF4D is expressed in many tissues, including brain, where it is detected in the nervous system, specifically in myelinated axons and ependymal cells. IGSF4D is localized to the plasma membrane as a single-pass membrane protein and is expressed as three isoforms. IGSF4D functions in the regulation of cell–cell adhesion by homophilic and heterophilic interactions leading to cell aggregation. These interactions are also important for neuron–neuron or neuron–glia associations, which are important for the development and function of the central nervous system. IGSF4D is downregulated in lung cancer, suggesting a possible role in tumor suppression.