Prominin-1 (alias CD133, PROML1; NCBI accession number: NM_006017, human; NM_008935, mouse; NM_021751, rat) is a membrane glycoprotein specifically associated with plasma membrane protrusions. It displays a unique membrane topology with five membrane-spanning domains and two large N-glycosylated extracellular loops (over 250 residues each). After the cleavage of the signal peptide, the N-terminal domain is exposed to the extracellular space whereas the C-terminal domain resides in the cytoplasm (Fig. 1 A)(Corbeil et al., 2001). Prominin-1 has been found in any metazoan species analyzed. Relatives have been found in other vertebrate classes such as birds and fish and in various invertebrates including insects and worms. Although a low percentage of amino acid identity is observed among vertebrate and invertebrate prominin-1, multiple sequence analysis revealed a conserved cysteine-rich domain located in the transition of the first transmembrane segment and the first cytoplasmic loop and leucine zipper-like motifs in the extracellular loops. The physiological relevance of these domains remains to be defined. ThePROMININ-1gene is located on chromosome 4p15. 32 in human (NCBI gene 8842), 5B3 in mouse (NCBI gene 19126) and 14q21 in rat (NCBI gene 60357). The genomic organization is strikingly similar in all three species. The PROMININ-1 gene is composed of at least of 37 exons that span more than 150 kb, and is under the control of five alternative promoters (Fargeas et al., 2006). To date, eight prominin-1 splice variants affecting the open reading frame have been identified, and several of them exhibit distinct C-terminal domains. A typical prominin-1 molecule comprisesz850 amino acid residues with an apparent molecular mass of z115e120 kDa including glycosylation.