PR domain containing 16 (PRDM16) is a transcription coregulator that plays a role in the development of left ventricular noncompaction cardiomyopathy (LVNC) and dilated cardiomyopathy (DCM) in humans. Our group and others demonstrated that Prdm16 is a crucial regulator of cardiac gene expression during heart development, and its loss caused LVNC and DCM in mice. Moreover, we showed that conditional deletion of Prdm16 in the mouse heart resulted in sex-specific LVNC and DCM phenotypes, with females experiencing more severe outcomes and reduced survival. Recent findings indicate that during cardiac development, sex-specific gene expression patterns may significantly contribute to differences in cardiac structure, function, and metabolic maturation between males and females. These developmental differences have been identified in early embryonic stages, before sex hormone production, and involve autosomal and sex chromosome genes. However, the extent to which transcriptional mechanisms contribute to sex differences in the diseased heart remains unclear. Therefore, exploring sex-biased cardiac gene regulation is necessary not only for understanding how Prdm16 governs cardiac development and maturation in a sex-specific manner, but also for developing precise therapeutics tailored to specific patients during the treatment of CVD. This study aims to investigate sex-specific gene transcription and regulation by Prdm16. We hypothesize that Prdm16 regulates sex-specific genes with differential involvement in cardiac development.