Dear Editor,Congenital heart disease (CHD) is a major birth defect worldwide.However,the aetiology of CHD remains unclear and the detailed molecular mechanisms underlying CHD pathogenesis have not been fully understood.The human regulator of calcineurin (RCAN1) gene is highly expressed in human hearts and brains (Fuentes et al.,1995) and composed of seven exons that are altematively spliced and/or transcribed by differential promoters to produce different isoforms (Fig.1A) (Yang et al.,2000).RCAN1.1(NM_004414) and RCAN1.4 (NM_203418) are the two major isoforms differentially expressed in many tissues and cells.RCAN1.1 is constitutively expressed while the expression of RCAN1.4 is induced by diverse stimuli (Yang et al.,2000;Lange et al.,2004).RCAN1.4 negatively regulates NFAT-mediated transcription (Lange and Yutzey,2006;Qin et al.,2006),which is an important regulator for early heart development (de la Pompa et al.,1998).Although SNPs rs149048873,rs193289374 and rs143081213 in the RCAN1.1 promoter were not associated with sporadic CHD (Guo et al.,2015;Li et al.,2015),the function of RCAN1.4 in CHD remains elusive.