Our study in pressure‐overload induced HF in mice demonstrated the following: (1) Decreased HINT2 expression in failing hearts, indicating its role in cardiac remodelling and stress response; (2) Protective effects of HINT2, evidenced by improved heart function and reduced damage markers with HINT2 overexpression, and intensified cardiac dysfunction with HINT2 deficiency. The gene discussed is HINT2; the disease is hydrops fetalis.