msk, myocardial SNF1-like kinase, was originally isolated in a screen for kinases expressed during early cardiogenesis in the mouse. msk maps to the proximal end of mouse chromosome 17 in a region that is syntenic with human chromosome 21q22.3, where the gene for SNF1LK, a predicted protein that shares 80% identity at the amino acid level with Msk, is located. Accordingly, msk has been redesignated snf1lk. Interestingly, the region encompassing the SNF1LK locus has been implicated in congenital heart defects often observed in patients with Down syndrome. snf1lk is also expressed in skeletal muscle progenitor cells of the somite beginning at 9.5 dpc. These data suggest a more general role for snf1lk in the earliest stages of muscle growth and/or differentiation. Consistent with a role in cell cycling, we observe that Chinese hamster ovary cells that express a tetracycline-inducible SNF1LK kinase domain do not divide, but undergo additional rounds of replication to yield 8N and 16N cells. These data suggest a possible function for SNF1LK in G2/M regulation. We show data that indicate that SNF1LK does not share functional homology with other SNF1-related kinases, but represents a new subclass with novel molecular activities.