The control of cofilin-1 phosphorylation on Thr25, in addition to its effect on actin dynamics, directly regulates MRTF-A/SRF signaling activity in cardiac cells and an imbalance in this regulation ultimately leads to cardiac disease associated with mutations in LMNA. Our results also broaden our knowledge of diseases related to cofilin-1, as we demonstrate that cofilin-1 participates in the pathogenesis of left ventricular dysfunction through the transcriptional control of ATAT1 driving α-tubulin acetylation. This evidence concerns the gene CFL1 and heart disorder.