UL16-binding protein 5 (ULBP5)

UL16-binding protein 5 (ULBP5), also known as RAET1G, is a human MHC class I–related, stress‑induced cell‑surface ligand that binds and activates the NKG2D (KLRK1) receptor on natural killer cells and subsets of T cells. It belongs to the UL16‑binding protein family identified by their interaction with the HCMV glycoprotein UL16 and the broader group of human NKG2D ligands involved in immunosurveillance of infected and malignant cells. As with other ULBPs, its expression and availability at the cell surface can be regulated by viral immune evasion (intracellular retention by HCMV UL16) and by proteolytic processing mechanisms described for related ligands, which affect NKG2D‑mediated cytotoxic responses.

Other names

Retinoic acid early transcript 1G (RAET1G)NKG2D ligand (human) family member; part of the UL16‑binding proteins (ULBPs) familyUnique long 16 binding protein 5

Therapies targeting this axis generally act by: - Enhancing NKG2D–ligand engagement to promote NK/T‑cell cytotoxicity - Inhibiting proteolytic shedding of NKG2D ligands (e.g., metalloprotease inhibition shown for ULBP2/MICA) to increase surface ligand density - Blocking viral immunoevasins (e.g., HCMV UL16) that retain selected NKG2D ligands intracellularly