Congenital dilated cardiomyopathy (cDCM) is a rare condition in which infants suffer heart failure in the absence of obvious causes such as toxins, infection/inflammation, global metabolic derangements, or gross structural defects. While the pathophysiology of cDCM is unclear, genetic etiologies have been suspected. The Hong Lab has found that mutations in the gene RTTN encoding the centrosome protein Rotatin causes poor contractile function in an induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) model. Interestingly, this mutation also causes centrosome defects and aberrant CM proliferation. We hypothesize that the iPSC-CM model can be implemented to discover new therapeutic strategies for cDCM and other heart diseases. Previously, we found that certain small molecules (SMs) that modulate Hippo signaling pathways can reverse the cDCM phenotype in the iPSC-CMs model. In an independent set of experiments, the Hong lab and collaborators found that a novel small molecule Wnt inhibitor LRN11 inhibits proliferation and may promote maturation of CMs, while another novel small molecule, named LRN9, promotes proliferation in wild-type CMs. To confirm these findings and to observe their effects on proliferation at different stages of CM differentiation, we treated human iPSC-CMs with the small molecules after 13, 23, 33, and 43 days of differentiation. The results somewhat replicated the earlier finding for LRN9 and LRN11 on CM proliferation, but they are not conclusive. To assess the effects of LRN9 and LRN11 on proliferation in non-CMs, we tested LRN9 and LRN11 on several cancer cell lines. Our initial results indicate that the small molecules either do not affect the proliferation of these non-CMs or affect them in a way that we cannot explain. Based on these promising preliminary results, we hypothesize that compounds such as LRN11 may be therapeutic for cDCM while LRN9 may be therapeutic as a regenerative therapy to replace heart tissue lost to heart attacks without promoting cancer formation.