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They are <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>a<jats:sup>2+<\/jats:sup> release channels found primarily on the sarcoplasmic reticulum of myocytes. Several hundred mutations in <jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>y<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>s are associated with skeletal or cardiomyocyte disease in humans. Many of these mutations can now be mapped onto the high resolution structures of individual <jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>y<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content> domains and on full\u2010length tetrameric cryo\u2010electron microscopy structures. 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