Silencing of either Epac or Rap1a did not reciprocally alter ESRP1 expression, confirming an upstream regulatory hierarchy.<h4>Conclusion</h4>Our findings demonstrate that ESRP1 upregulation in alveolar epithelial cells drives IPF progression by promoting EMT via the Epac-Rap1a axis. Here, ESRP1 is linked to idiopathic pulmonary fibrosis.