NCAM1 belongs to the immunoglobulin superfamily of adhesion molecules. A wide range of alternatively spliced NCAM1 messenger RNAs (mRNAs) has been described to date, but only the 120-, 140-, and 180- kDa isoforms are commonly expressed. NCAM1 plays an important role in the regulation of neurogenesis, neurite outgrowth, proliferation, and cell migration, however, its function in hematopoiesis, including NK cells, is poorly understood. NCAM1 signaling is mediated either by homophilic or heterophilic interactions with fibroblast growth factor receptor (FGFR), L1-CAM, N-cadherin and other components of the extracellular matrix. Upon activation, NCAM1 triggers a variety of signaling cascades including FYN–focal adhesion kinase (FAK), MAPK, and phosphatidylinositol 3-kinase (PI3K) pathways.