The uncoupling protein 1 (UCP1) is the first uncoupling protein described. It belongs to the family of the mitochondrial carrier proteins and is expressed mainly in the brown adipose tissue. Recently, the family of the UCPs has rapidly been growing due to the successive cloning of UCP2, UCP3, UCP4 and UCP5, also called BMCP1 (brain mitochondrial carrier protein-1). Phylogenetic studies suggest that UCP1/UCP2/UCP3 on one hand and UCP4/UCP5 on the other hand belong to separate subfamilies. In this study, we report the cloning from a frog Xenopus laevis (Xl) oocyte cDNA library of a novel UCP that was shown, by sequence homology, to belong to the family of the ancestral UCP4. This cloning provides a milestone in the gap between Drosophila melanogaster or Caenorhabditis elegans on one hand and the mammalian UCP4 on the other. Xl UCP4 is already expressed in the oocyte, being the first uncoupling protein described in the germ cell lineage. During development, it segregates in the neural cord and in the adult, in situ hybridization shows its expression in the neurons and also in the choroid plexus of the brain. By RT-PCR analysis, it was found that Xl UCP4 is present in all the subdivisions of the brain and also that it differs from mammalian UCP4 by a very high relative level of expression in peripheral tissues such as liver and kidney. The peripheral tissue distribution of Xl UCP4 reinforces the hypothesis that UCP4 might be the ancestral UCP from which other UCPs diverged from.