Synaptic cell adhesion molecule (SynCAM) mediates homophilic cell-cell adhesion in a Ca2+-independent manner. SynCAM also mediates heterophilic cell-cell adhesion with CADM3 and PVRL3 in a Ca2+-independent manner. SynCAM acts as a tumor suppressor in non-small-cell lung cancer (NSCLC) cells. SynCAM’s interaction with CRTAM promotes natural killer (NK) cell cytotoxicity and interferon-gamma (IFN-gamma) secretion by CD8+ cells in vitro as well as NK cell-mediated rejection of tumors expressing CADM3 in vivo. SynCAM contributes to the less invasive phenotypes of lepidic growth tumor cells. In mast cells, SynCAM mediates attachment to and promotes communication with nerves. CADM1, together with MITF, is essential for development and survival of mast cells in vivo. SynCAM plays diverse roles in spermatogenesis including in the adhesion of spermatocytes and spermatids to Sertoli cells and for their normal differentiation into mature spermatozoa.