Mediator complex: update of key insights into transcriptional regulation of ancestral framework and its role in cardiovascular diseases.

Transcriptional regulation plays a pivotal role in coordinating the complex morphogenetic and molecular events involved in heart development and function. In the early stages of cardiovascular diseases (CVDs), the Mediator complex (MED) performs a variety of essential functions. While initial studies focused on correlating MED components with specific CVDs, more recent research has shifted toward a deeper exploration of the MED's role in the early pathogenesis of these diseases. This review highlights the latest findings published between January 2018 and February 2025, with a particular focus on the protein subunits MED1, MED12, MED13, MED13L, MED15, and MED23, and their implications in various cardiovascular pathologies. The MED complex is a crucial regulator of gene transcription, bridging transcription factors and RNA polymerase II. In "-omic" sciences, studying MED functions is essential to understanding molecular interactions that regulate gene expression. Within precision medicine, the MED complex is a key node in gene expression networks. Its study within the -omic framework can provide valuable insights into how molecular interactions shape cellular processes in both health and disease, ultimately enhancing the diagnosis, understanding, and treatment of CVDs through personalized medicine.