Using a fluorescent donor probe on actin and an acceptor probe on myosin’s ELC, together with unique high-performance TR-FRET instrumentation [29], this work has provided direct insight into the ATP-driven structural transitions within the actin-myosin complex, as influenced by isoforms of ELC [26] and cardiomyopathy mutations in the ELC [27]. Here, MYH14 is linked to cardiomyopathy.