RAET1L (retinoic acid early transcript 1L) encodes a cell surface glycoprotein that functions as a ligand for the NKG2D receptor (KLRK1), playing a crucial role in immune surveillance 1. The protein is one of eight human NKG2D ligands and binds to the activating receptor NKG2D expressed on natural killer (NK) cells, CD8+ T cells, and other immune cell subsets 12. RAET1L is a GPI-anchored glycoprotein that activates immune cells upon binding to NKG2D, leading to cytotoxic responses against tumor cells and viral-infected cells 23. Expression is tightly regulated and typically absent in healthy adult tissues but can be induced by cellular stress, hyperproliferation, transformation, or pathogen infection 1. The gene exhibits significant polymorphism, with multiple allelic variants identified across different populations 345. Clinical studies demonstrate that RAET1L polymorphisms have important therapeutic implications, with specific alleles associated with improved outcomes in allogeneic stem cell transplantation 6 and response to neoadjuvant chemoradiotherapy in rectal cancer 7. The protein can also be targeted by viral immune evasion mechanisms, such as CMV UL16 protein retention 2.