ULBP6, also known as RAET1L and N2DL-6, belongs to the MHC class I-related proteins of the RAET1 family. ULBP6 is a glycoprotein containing extracellular α-1 and α-2 domains, but lacking the membrane proximal Ig like α-3 domain, anchored to the membrane via glycosylphosphatidylinositol (GPI) linkage. ULBP6 is widely expressed on the surface of epithelial cells, endothelial cells, and immune cells, with upregulated expression under stress or tumor conditions. Its core function is to bind to the NKG2D receptor on NK cells, activating their cytotoxic activity, participating in innate immune surveillance, and regulating immune responses in the tumor microenvironment. Currently, it is regarded as a potential immunotherapeutic target for tumors such as melanoma and lung cancer, exerting therapeutic effects by enhancing NK cell-mediated tumor killing.