RHBG (Rh family B glycoprotein) is a mammalian ammonium transporter that mediates transepithelial ammonia handling and acid-base homeostasis 1. The protein functions primarily as an electrogenic NH4+ transporter, though it can transport both NH4+ and NH3 species across basolateral plasma membranes of epithelial cells 2. Beyond ammonia transport, RHBG exhibits dual functionality as a transceptor—it also transports CO2 and initiates intracellular signaling through MyD88-dependent NFκB activation in response to ammonia, independent of canonical toll-like receptor mechanisms 23. In the kidney, RHBG localizes to α-intercalated cells of the collecting duct via tyrosine-based sorting signals and ankyrin-G anchoring 4. Notably, while RHBG is expressed in rodent kidneys and skeletal muscle 5, it is not detectable in normal human kidney tissue, where RhCG serves as the primary ammonia transporter 6. RHBG expression in cancer cells is regulated by Wnt/β-catenin-TCF4 signaling 7, linking it to tumorigenesis. The protein's dual transport-signaling properties suggest distinct therapeutic targets for managing hyperammonemia and potentially modulating cancer cell metabolism.