Thus, ARL2 has been shown to have a distinct and essential role in mitochondria that expands its known roles in eukaryotic cell biology. These roles at least provide an opportunity for coordinate regulation of energy metabolism and the cytoskeleton, with likely links to cell division. Together, our data lead us to propose the existence of two actions of ARL2 relevant to mitochondrial physiology that are each distinct from effects on tubulin or microtubules; one impacting inner membrane ultrastructure with consequences to ATP production and one involving ELMOD2 that Tirofiban results in changes in morphology and motility. These models are discussed in more detail below. The effects of ARL2 siRNAs on ATP pools are consistent with the previously described effects of microRNAs that target ARL2 and lead us to conclude both that ARL2 is required for maintenance of ATP levels and that at least some tissues have the means to modulate ARL2 levels post-transcriptionally. Four or more microRNAs may target ARL2 mRNA in cardiac tissues, and depletion of ARL2 in neonatal ventricular myocytes also lowered ATP levels. Earlier, we found that levels of mitochondrial ARL2 increased several fold in mice deleted for the adenine nucleotide transporter, ANT1, but only in cardiac and skeletal muscle, indicating the existence of regulated Benzoic Acid import of ARL2 into mitochondria that may be tissue specific. With the levels of cellular ARL2 under regulation by miRNAs; the regulated import of ARL2 into mitochondria, via unknown mechanisms; and the ancient and highly conserved nature of ARL2 and its ubiquitous expression, we believe that ARL2 plays fundamental roles in energy metabolism in mitochondria of all eukaryotic cells, though ARL2 function may be particularly important in those cells with high energy demands, e.g., cardiac and skeletal muscle cells. This requirement for ARL2 in the maintenance of ATP pools may explain its essential nature, previously described in a number of organisms, though in those studies clear resolution from effects on microtubules and cell division was not achieved.