This study found that activation of the ATF4-dependent serine biosynthesis pathway and TRIB4 kinase signaling using a specific combination of small molecule kinase inhibitors (SMKIs) was able to attenuate the dilated cardiomyopathy phenotype in iPSC-CMs by establishing a screening model for dilated cardiomyopathy iPSC-CMs, whereas inhibition of the serine biosynthesis biosynthetic pathway or PHGDH exacerbated contractile dysfunction in dilated cardiomyopathy iPSC-CMs. Here, ATF4 is linked to dilated cardiomyopathy.