Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a hereditary heart disease characterized by bidirectional or polymorphic ventricular tachycardia and an increased risk of sudden cardiac death. Although trans-2,3-enoyl-CoA reductase like () is a newly reported pathogenic gene leading to CPVT that can influence intracellular calcium regulation, the unidentified mechanism underlying the pathogenesis of TECRL deficiency-mediated CPVT remains mainly elusive. In the present study, knockout (KO) mice were established and the differentially expressed genes (DEGs) were investigated by RNA-sequencing from the heart tissues. In addition, 857 DEGs were identified in KO mice. Subsequently, a weighted gene co-expression network analysis was conducted to discern the pivotal pathways implicated in the -mediated regulatory network. Moreover, pathway mapping analyses demonstrated that essential metabolism-related pathways were significantly enriched, notably the fatty acid metabolic process and calcium regulation. Collectively, the data suggested a synergistic relationship between deficiency and cardiometabolic and calcium regulation during the development of CPVT. Therefore, further studies on the potential function of TECRL in cardiac tissues would be beneficial to elucidate the pathogenesis of CPVT.