This review describes the current state of knowledge of the Raph blood group system, which consists of a single antigen, MER2. MER2 was initially classified as a high-incidence antigen in the 901 series of blood groups, formerly known as 901011, but was reclassified as an antigen in the Raph blood group system in 2004. There have been six reports of human alloantibodies to MER2. Three of the subjects were found to have a stop codon in the CD151 gene, which encodes a member of the tetraspanin family of proteins. These three individuals had nephropathy and deafness, and two of the three, who are siblings, also had skin lesions and P-thalassemia minor. The fourth subject had missense mutation c.533G>A (p.Argl78His). Subjects 5 and 6 shared missense mutation c.511C>T (p.Argl71Cys) as well as a synonymous single-nucleotide mutation (c.579A>G) and had no clinical features. Although the CD151 protein is critical to cell- to-cell interactions and cell signaling and is implicated in cancer progression, the significance in transfusion medicine is limited to one report of a hemolytic transfusion reaction in Subject 5.