Animal experiments further confirmed that curcumin improved HF by regulating the Crispld2/PI3K/AKT axis.<h4>Conclusions</h4>This study elucidates the molecular mechanism by which curcumin exerts anti-HF effects by inhibiting the activation of the PI3K/AKT pathway mediated by Crispld2, providing a new strategy for targeted therapy of Crispld2. The gene discussed is CRISPLD2; the disease is hydrops fetalis.