XKRX (XK related X-linked) is an X-chromosome X that belongs to the XK family of putative membrane transporters 1. Members of the XK family, including XKRX, share structural similarity with XK, a component of the Kell blood group system complex, and are predicted to have similar membrane topology 1. Unlike the ubiquitously expressed XK protein, XKRX represents a more specialized family member with distinct evolutionary origins 1. Evolutionarily, XKRX/Y represents an ancient gametolog pair that differentiated in the therian ancestor, with molecular analyses indicating concurrent divergence timing shared with other sex-chrX gene pairs including SOX3/SRY and RPS4X/Y 2. In clinical context, XKRX has been identified as an independent prognostic risk factor for colorectal cancer (CRC) survival, serving as one of twenty immune-related genes incorporated into machine learning-based survival prediction systems 3. These prognostic models achieved strong predictive performance (concordance index 0.852 for 1-year survival) for identifying CRC patients at high risk of poor prognosis 3. However, the specific molecular function and substrate of XKRX remain undefined, requiring further investigation to clarify its role in immune regulation and cancer biology.