The article discusses the connection between actin dynamics and gene transcription in driving cellular motility. It highlights the role of the actin–MRTF–SRF circuit in linking cytoskeletal changes to gene expression. Actin polymerization releases MRTF cofactors, which activate SRF to regulate genes involved in actin dynamics. This system is crucial for cell motility, which is regulated by both physiological and pathological stimuli. The article reviews various signaling pathways, including those involving G protein-coupled receptors, receptor tyrosine kinases, integrins, TGFβ, E-cadherin, and non-canonical Wnt signaling, that modulate actin dynamics and gene expression. It also discusses the role of nuclear actin and ABPs in gene regulation, as well as the involvement of miRNAs in modulating SRF and MRTF activity. The article concludes that the actin–MRTF–SRF circuit is essential for cellular motility and has implications for diseases such as cardiovascular disorders and cancer. The study emphasizes the importance of understanding the interplay between actin dynamics and gene expression in cellular functions and disease processes.The article discusses the connection between actin dynamics and gene transcription in driving cellular motility. It highlights the role of the actin–MRTF–SRF circuit in linking cytoskeletal changes to gene expression. Actin polymerization releases MRTF cofactors, which activate SRF to regulate genes involved in actin dynamics. This system is crucial for cell motility, which is regulated by both physiological and pathological stimuli. The article reviews various signaling pathways, including those involving G protein-coupled receptors, receptor tyrosine kinases, integrins, TGFβ, E-cadherin, and non-canonical Wnt signaling, that modulate actin dynamics and gene expression. It also discusses the role of nuclear actin and ABPs in gene regulation, as well as the involvement of miRNAs in modulating SRF and MRTF activity. The article concludes that the actin–MRTF–SRF circuit is essential for cellular motility and has implications for diseases such as cardiovascular disorders and cancer. The study emphasizes the importance of understanding the interplay between actin dynamics and gene expression in cellular functions and disease processes.