DNAM-1 is a member of the Ig superfamily, encoded by a gene on human chromosome 18q22.3, is expressed by human NK cells, T cells, a subset of B cells, monocytes and platelets. Interactions between DNAM-1 on NK cells and its ligands on tumour cells augments the NK cell–mediated cytotoxicity and cytokine production. CD155 and its related family member CD112, the known ligands for DNAM-1, broadly expressed on hematopoietic, epithelial, and endothelial cells. Moreover, it was shown that the interaction of DNAM-1 with CD112 and CD155 contributes to the NK-mediated lysis of both imDCs and mDCs. Dysregulation of DNAM-1 is associated with susceptibility to juvenile idiopathic arthritis, type 1 diabetes (T1D), lupus, and rheumatoid arthritis in patients.