Our dual-omics analysis (translatome and proteome) of E18.5 embryonic hearts from global Prrc2b knockout and wild-type control mice, including polysome-seq and mass spectrometry, suggests that the loss of function of PRRC2B causes aberrant gene expression in cell proliferation, migration, and artery development, thereby leading to congenital heart defects. Here, PRRC2B is linked to congenital heart disease.