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Striated muscle cells contain a specialized membrane system, the sarcoplasmic reticulum (SR), which regulates calcium homeostasis and contraction. However, the biochemical and physiological relationship between the ER and SR, as well as the extent to which both compartments contribute to protein synthesis, remain incompletely understood. Quantification of ER\u2010 and SR\u2010associated proteins in isolated ventricular cardiac myocytes revealed that the relative abundance of ER\/SR\u2010resident protein quality control components and ribosomes decreased during postnatal maturation, whereas SR\u2010associated Ca\n 2<\/jats:sup>\n +<\/jats:sup>\n \u2010handling proteins increased. Immunocytochemistry revealed that the membrane compartment prominent in early postnatal stages exhibits predominantly ER characteristics and diminishes during postnatal development. In adult cardiac myocytes, the SR becomes the dominant membrane network throughout the cell, while ER markers remain enriched in the perinuclear region. Immunocytochemistry further indicated that the ER and SR perform overlapping yet distinct specialized functions, with excitation\u2013contraction coupling localized to the SR, and initiation of secretion concentrated within the ER. In adult ventricular cardiac myocytes, ribosomes and mRNA localize adjacent to both the ER and SR, indicating their roles as direct sites of localized protein synthesis and homeostasis. These findings demonstrate that molecular differentiation and structural organization of the ER\/SR during cardiac muscle development culminate in a specialized protein synthesis network within the sarco\/endoplasmic reticulum of adult myocytes.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n Although the sarcoplasmic reticulum (SR) is the established centre for calcium regulation in striated muscle, its role in membrane and secreted protein synthesis has remained unknown.<\/jats:p>\n <\/jats:list-item>\n \n It has remained unclear whether the endoplasmic reticulum (ER) and SR coexist as distinct membrane networks in cardiac myocytes or whether they form a single system that fulfills both calcium\u2010handling and protein synthesis functions.<\/jats:p>\n <\/jats:list-item>\n \n We found that postnatal cardiac maturation involves a major reorganization in which the centralized, ER\u2010dominant network of neonatal myocytes is replaced by an expansive, SR\u2010dominant network in the adult cell periphery, while ER markers become largely confined to the perinuclear region.<\/jats:p>\n <\/jats:list-item>\n \n Using stimulated emission depletion super resolution microscopy and electron microscopy, we demonstrated that active ribosomes and mRNA associate with the longitudinal SR but are spatially excluded from ryanodine receptor 2\u2010rich junctional zones.<\/jats:p>\n <\/jats:list-item>\n \n Our results establish that the SR functions as a specialized, distributed protein synthesis network that enables adult cardiac myocytes to maintain their highly organized cellular architecture through localized translation.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n 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