The proposed project leverages our longstanding partnership with the Family Heart Foundation (FHF), a nonprofit research and advocacy organization, to refine and test two promising approaches to implement cascade screening in individuals with familial hypercholesterolemia (FH). Despite evidence-based guidelines for FH diagnosis and treatment, over 1 million Americans with this inherited condition remain undiagnosed. Cascade screening is an evidence-based practice of contacting and screening first-degree biological relatives of FH probands, improves timely FH diagnosis, and reduces morbidity cost-effectively. Cascade screening programs have been successful in other countries where health systems play a key role in notifying relatives, but major implementation challenges limit uptake in the U.S. Pilot projects have identified hurdles including regulatory constraints limiting health system outreach and difficulty contacting family members outside a given health system. In the U.S., cascade screening must involve the proband given regulatory constraints. Applying advances in behavioral economics has great potential to improve implementation of cascade screening via proband-mediated strategies. Led by MPIs with expertise in implementation science (Beidas), behavioral economics (Volpp), and FH (Rader), we have co-designed, and will pilot and test two patient-facing implementation strategies to increase reach of cascade screening with 300 probands from Penn Medicine. Our randomized controlled trial will test (a) a health system-mediated strategy using automated text messages, (b) a Family Heart Foundation-mediated strategy using a navigator, and (c) the “usual care” approach to cascade screening. Both active strategies will be informed by behavioral economics. In the R61 phase, we co-designed health system- and FHF-mediated implementation strategies using behavioral economics in partnership with the FHF and key stakeholders (Aim 1) and are piloting our strategies with 20 F