Fibroblast growth factor homologous factors (FHFs) bind to the cytoplasmic C-terminus of voltage-gated sodium channels (VGSCs) and modulate channel function. Variants in FHFs or VGSCs perturbing that bimolecular interaction are associated with arrhythmias. Like some channel auxiliary subunits, FHFs exert additional cellular regulatory roles, but whether these alternative roles affect VGSC regulation is unknown. Using a separation-of-function strategy, we show that a structurally guided, bindi...
