Facilitating endogenous cardiomyocyte proliferation has emerged as an important strategy for cardiac repair. Conserved retinol saturase (Retsat) functions in producing all-trans 13,14-dihydroretinol in the endoplasmic reticulum (ER). However, Retsat's role and mechanism in heart regeneration remain unclear. Here, we uncover that Retsat is upregulated in cardiomyocytes during cardiac regeneration in mice. Cardiomyocyte-specific