However, the assay that we have developed and the identification of the time frame for activation and inactivation of Rac1 by cell-cell adhesion provide the basis for a screen to identify candidates. The recent identification of the Dermokine gene came from different studies carried out to identify new genes specifically expressed during the late stage of epidermis differentiation. Mapped to human chromosome 19q13.1, Dmkn spans 25 exons. Its expression leads to four groups of transcripts according to three different transcriptional start sites, two transcriptional termination sites, and several alternative coding exons. The corresponding isoforms were named a, b, c and d. The d transcripts, spanning from exon 6 to exon 25, are radically different from the a, b and c transcripts. First, they show a very broad pattern of expression, including numerous tissues and organs, whereas a, b and c mRNAs expression is mainly restricted to epidermis. Second, unlike a-, b- and c-groups, d mRNAs do not encode a putative signal peptide and are predicted to produce cytosolic proteins. This was confirmed by the expression of recombinant Dmknd in transfected 293/EBNA cells. Finally, the d family of transcripts is represented by a surprisingly broad number of members. We cloned up to 9 different cDNAs from human epidermis, potentially encoding 6 different Dmknd proteins. Rab proteins make up the largest subfamily of small GTPases that play central roles in intracellular membrane trafficking. So far, in humans, the Rab family has been shown to have more than 60 proteins scattered around distinct intracellular compartments, where they regulate vesicle budding, transport and GSI-IX fusion. Rab proteins cycle between an active and an inactive state. The nucleotide switch leads to a Rab conformational change which determines the interaction with specific regulators and effectors that are located both on membranes and in the cytosol. For example, the GDP/GTP exchange factors catalyze the conversion from the GDP- to GTP-bound state, whereas GTPase-activating proteins catalyze GTP hydrolysis. Among the Rab family of proteins, Rab5 is a key player in the early endocytic pathway. It regulates clathrin-coated vesiclemediated transport from the plasma membrane to the early endosomes as well as homotypic early endosome fusion. Moreover, it has also been implicated in endosome motility along microtubules and actin filaments and also in growth factor signalling. The three Rab5 paralogues Rab5a, b and c, encode isoforms showing distinct tissue distributions. At least 20 cytosolic proteins specifically interact with active Rab5, highlighting the complexity of the downstream regulation by this GTPase. The Dmknd share no sequence similarity with any known protein. In order to elucidate its role we thus performed yeast twohybrid screening and identified the Rab5 proteins as partners.