In previous studies we have found that membrane proteins with few transmembrane (TM) helices are less studied than other. This is particularly true for 2TM proteins where more than 70% of the about 700 proteins remained unclassified. Interestingly, we found evidence for several uncharacterized homologues to a small group of genes known as the Interferon-induced transmembrane proteins (IFITM) family. The IFITMs constitute a group with four human members (IFITM1-3, 5) that are found in a consecutive order on chromosome 11, having two transmembrane (2TM) helices. The IFITM4 gene is not present in human, but is located in proximity to the other four genes in the mouse genome. The IFITM1-3 proteins were identified 25 years ago as being upregulated by interferons (IFN) [6] . Recently they received considerable attentions as IFITM1-3 were found to prevent infection of a growing list of viruses such as HIV-1, SARS influenza A H1N1, West Nile and Dengue fever viruses [7, 8, 9, 10] . Hence, proteins of the IFITM family mediate part of the antiviral response orchestrated by IFNs. However, the IFITM family is also involved in other processes such as oncogenesis, bone mineralization (IFITM5) and germ cell development (IFITM1 and 3) and IFITM5 has not been identified as interferon-inducible [11, 12, 13, 14] . Although the biological roles of the IFITM genes are emerging, no thorough evolutionary analysis has been performed on this group.