Targeting Ca2+ dysregulation in HF and arrhythmias has long been investigated as a potential therapeutic target and, as is evident from this review, there is considerable current research investigating targeting proteins associated with Ca2+ handling, including RyR2, NCX, SERCA, and TRP channels, as a therapeutic approach for cardiomyopathy, HF and arrhythmias. This evidence concerns the gene TLX2 and cardiomyopathy.