part to the long lever arm formed by its neck domain and stable alpha helix, and in part due to the remarkably large swing of ~120° the Myo10 lever arm undergoes during its power stroke. There is much interest in the mechanisms that target Myo10 to filopodial actin bundles, and in Myo10’s ability to step from one actin filament in a bundle to another. In addition to the full-length Myo10 described above, the use of alternative transcription start sites located in intron 19-20 of the full-length transcript results in the production of “headless” Myo10 transcripts that lack most of the myosin head domain, but include the rest of the Myo10 heavy chain. The major headless transcripts in human are predicted to include exons 20-41 of full-length MYO10 and initiation of translation at M644 would result in a 1415 amino acid headless protein with a predicted MW of ~163 kDa that would be identical to amino acids 644-2058 of full-length MYO10. Because headless Myo10 lacks most of the head domain, it lacks motor activity, but it retains all of Myo10’s other domains and is thus expected to retain the ability to bind to light chains of the calmodulin superfamily, to membranes containing PI(3,4,5)P3 or PI(4,5)P3, to microtubules, and to proteins that bind the Myo10 tail such as DCC, neogenin, and β-integrins. Headless Myo10 has been hypothesized to act as a scaffolding protein for its various binding partners and/or as a “natural” dominant negative that can inhibit the actions of full-length Myo10. Evolutionary relationships Myo10 is a member of an evolutionarily ancient group of myosins whose tails contain MyTH4-FERM domains and that have been shown to have important functions in cellular protrusions based on actin bundles such as filopodia, microvilli, and inner ear stereocilia. The slime mold Dictyostelium expresses a MyTH4-FERM myosin known as myosin-7 that is involved in filopodia formation and has 2 MyTH4-FERM supramodules but no PH domains. Myo10 appears to have originated from an ancestral myosin-7-like protein approximately a billion years ago by several changes including loss of 1 MyTH4-FERM supramodule and addition of 3 PH domains. A Myo10 gene is present in organisms ranging from filozoans and choanoflagellates (the protozoan groups most closely related to multicellular animals) to humans. Myo10 was lost in the invertebrate lineages leading to organisms such as fruit flies and nematodes, although these lineages do express other MyTH4-FERM myosins such as myosin-7. Humans express