Owing to resident myogenic progenitor cells (MPCs), skeletal muscle has a remarkable regenerative capacity in response to severe injury. Some of the factors underlying this capability have been identified, among them the forkhead transcription factor Foxk1, but the molecular networks that govern the regeneration of MPCs are not well understood. On page 5329, Daniel Garry and colleagues perform experiments that involve the knockdown and overexpression of Foxk1 in order to identify thus far unknown downstream targets in the myogenic lineage. They find that Foxk1 directly interacts with another forkhead transcription factor, Foxo4, and represses its transcriptional activity, resulting in the dysregulation of its target genes (such as the cyclin dependent kinase inhibitor p21) and, consequently, promoting cellular proliferation. In addition, they show that the Mef2 target genes that are regulators of differentiation, are also affected by perturbed Foxk1 expression, suggesting that Mef2 activity is modulated by Foxk1. Indeed, the authors find that Foxk1 interacts with Mef2c, which precludes it from activating the myogenic differentiation program. Taken together, their work demonstrates a dual role for Foxk1: it promotes MPC proliferation by repressing Foxo4 transcriptional activity and inhibits myogenic differentiation through the repression of Mef2, providing new insights into the transcriptional networks that regulate MPCs and their regeneration.