RHCE encodes the Rh blood group CcEe antigens, which are integral membrane proteins essential for erythrocyte membrane stability and function. The protein serves as a component of the ankyrin-1 complex, a multiprotein assembly that maintains erythrocyte membrane stability and shape 1. RHCE mediates the primary membrane attachment site for ankyrin-1 when associated with RHAG, and its distinct T-shaped conformation facilitates recognition and clustering of membrane proteins 1. The protein may participate in ammonium and carbon dioxide transport, suggesting a role in gas homeostasis. RHCE is organized into 10 exons spanning 75 kb, with alternative splicing producing different RNA isoforms 2. Expression is restricted to the erythroid/megakaryocytic lineage, controlled by erythroid-specific transcription factors including GATA-1 2. Clinical significance includes involvement in transfusion medicine, where RHCE variants can cause serological weaknesses and typing difficulties 3. The gene exhibits extensive polymorphism, with strong selection pressure maintaining variation between RHCE and RHD antigens 4. Disease associations include Rh-null syndrome, and accurate fetal RHCE genotyping from maternal blood is now possible for managing alloimmunization during pregnancy 5.