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Dysfunctional channel behaviour has been the subject of many investigations varying from single channel analysis through to complex animal models. This review discusses recent advances in the field, describes the controversy surrounding the exact consequences of RyR2 mutation and how the disparate data may be reconciled. This heterogeneity of function with respect to the effects of polymorphisms, phosphorylation, cytosolic and luminal Ca<jats:sup>2+<\/jats:sup> as well as inter\u2010domain interactions may have important implications for the recent pharmaceutical therapies which have been put forward. 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