Baugh et al. (2021) identified the first potent human SQOR inhibitor, with an IC50 of ∼29 nM. After structural optimization, this inhibitor exhibited high selectivity for SQOR over other mitochondrial enzymes, effectively avoiding off-target effects. In a mouse model of pressure-overload heart failure, the inhibitor significantly alleviated myocardial remodeling and dysfunction by inhibiting H2S degradation, demonstrating the feasibility of targeting the H2S metabolic pathway for treating heart failure. This evidence concerns the gene SQOR and heart failure.