In coming years, we will therefore witness an explosion of studies unravelling the contribution of epigenetic mechanisms to AF associated substrates such as gene regulatory networks linking DNA methylation and/or histone modifications to transcriptional regulation of key AF-associated transcription factors such as PITX2, TBX5, and ZFHX3 among others, or complex lncRNA–microRNA–mRNAs gene regulatory networks impacting on the electrophysiological and structural remodelling substrates underlying AF. This evidence concerns the gene TBX5 and atrial fibrillation.