Fibroblast growth factor homologous factors are potential ion channel modifiers associated with cardiac arrhythmias.

Stable electrical activity in cardiac myocytes is the basis of maintaining normal myocardial systolic and diastolic function. Cardiac ionic currents and their associated regulatory proteins are crucial to myocyte excitability and heart function. Fibroblast growth factor homologous factors (FHFs) are intracellular noncanonical fibroblast growth factors (FGFs) that are incapable of activating FGF receptors. The main functions of FHFs are to regulate ion channels and influence excitability, which are processes involved in sustaining normal cardiac function. In addition to their regulatory effect on ion channels, FHFs can be regulators of cardiac hypertrophic signaling and alter signaling pathways, including the protein kinase, NF<kappa>B, and p53 pathways, which are related to the pathological processes of heart diseases. This review emphasizes FHF-mediated regulation of cardiac excitability and the association of FHFs with cardiac arrhythmias and explores the idea that abnormal FHFs may be an unrecognized cause of cardiac disorders.