Here, we profiled the transcriptome and proteome of the hearts of the Tmem43 null mouse via RNA-Seq and mass spectral. Functional enrichments of the differentially expressed genes and differentially expressed proteins both revealed that the muscle contraction was the major pathway influenced by TMEM43 deficiency. Further study indicated that BMP2 signaling pathway and mitochondria may mediate TMEM43’s role in hearts. These results expand our knowledge of the roles of TMEM43 in hearts.