In contrast to the lack of activation of the calcineurin-NFAT pathway with TAC, an alternative Ca2+/CaM-dependent signalling pathway, the Ca2+/CaM-dependent protein kinase II (CaMKII)-histone deacetylase (HDAC)-myocyte enhancer factor 2 (MEF2) pathway (Backs et al., 2009; Backs et al., 2006; Passier et al., 2000), is activated in response to TAC (Yu et al., 2021). The gene discussed is HDAC9; the disease is persistent truncus arteriosus.