The Saccharomyces cerevisiae genome contains five P-type ATPases divergent from both of the well-known subfamilies of these membrane ion transporters. This newly recognized third subfamily can be further divided into four classes of genes with nearly equal relatedness to each other. Genes of this new subfamily are also present and expressed in multicellular organisms such as Caenorhabditis elegans and mammals; some, but not all, can be assigned to the classes identified in yeast. Different classes of genes and different genes within a class are expressed differentially in tissues of the mouse. The recently cloned gene for the mammalian aminophospholipid translocase belongs to this new subfamily, suggesting that other subfamily members may transport other lipids or lipid-like molecules from one leaflet of the membrane bilayer to the other.