Evidence regarding the role of these pathways during later stages of heart failure is controversial, however, as some reports suggest that IP3R and other Ca2+-handling proteins are downregulated at these stages35, while others have shown a redistribution of ryanodine receptor type 2 and sarco/endoplasmic reticulum Ca2+-ATPase type 2a as well as increased IP3R2 levels14. Here, RYR2 is linked to heart failure.