ARL15 is widely expressed [20]. However its function is unknown, and there have been no phenotypes previously associated with this gene. Based on its predicted protein sequence, ARL15 is structurally similar to ADP-ribosylation factors and Ras-related GTP-binding proteins which play key roles in the regulation of intracellular vesicle trafficking [19], and which have been specifically implicated in insulin signaling and insulin-stimulated glucose transport [21],[22],[23],[24]. Our preliminary data demonstrate that ARL15 is expressed in insulin-responsive tissues, including adipose tissue. Interestingly, expression was highest in skeletal muscle, which is the main site of insulin-mediated glucose disposal, but which does not synthesize adiponectin. Thus, ARL15 is a good candidate to be involved in cellular insulin resistance and/or adiponectin trafficking and secretion. Its implication in metabolic diseases by a non-hypothesis-based genetic approach provides strong impetus for further functional studies.
