At least half of all patients with heart failure primarily suffer from increased stiffening of the heart and impaired cardiac relaxation, rather than contractile dysfunction. The incidence of this form of heart failure, known as heart failure with preserved ejection fraction (HFpEF), steadily increases with aging, meaning that with an ever-increasing age of the general population, the medical and socioeconomic burdens of this disease will only continue to rise. Towards this end, the Ener-LIGHT consortium, composed of 4 researchers and clinicians, with extensive expertise in experimental and clinical cardiology, cell biology and immunology from 4 different European countries, will evaluate a novel therapeutic target for HFpEF that acts by activating cellular quality control mechanisms. Recently developed pharmaceutical and genetic interventions will be tested in preclinical models of the disease and available patient cohorts and biobanks will be used to assess the diagnostic and prognostic value of this novel molecular target. As such, the evidence generated from the project will directly feed into future clinical trials evaluating the efficacy of this potential therapy in patients with HFpEF