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However, the <jats:italic><jats:italic>in vivo<\/jats:italic><\/jats:italic> roles of POGLUT1 in the development, function, and maintenance of satellite cells are not well understood. Here, we show that conditional deletion of mouse <jats:italic><jats:italic>Poglut1<\/jats:italic><\/jats:italic> in myogenic progenitors leads to early lethality, postnatal muscle growth defects, reduced <jats:italic><jats:italic>Pax7<\/jats:italic><\/jats:italic> expression, abnormality in muscle extracellular matrix, and impaired muscle repair. <jats:italic><jats:italic>Poglut1<\/jats:italic><\/jats:italic>-deficient muscle progenitors exhibit reduced proliferation, enhanced differentiation, and accelerated fusion into myofibers. Inducible loss of <jats:italic><jats:italic>Poglut1<\/jats:italic><\/jats:italic> in adult satellite cells leads to their loss of quiescence and precocious differentiation, and impairs muscle repair upon serial injury. Cell-based signaling assays and mass spectrometric analysis indicate that POGLUT1 is required for the activation of NOTCH1, NOTCH2, and NOTCH3 in myoblasts and that NOTCH3 is a target of POGLUT1 like NOTCH1 and NOTCH2. These observations provide insight into the roles of POGLUT1 in muscle development and repair and the pathophysiology of LGMDR21.<\/jats:p>","DOI":"10.1371\/journal.pgen.1011806","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T17:53:09Z","timestamp":1755539589000},"page":"e1011806","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["The glycosyltransferase POGLUT1 regulates muscle stem cell development and maintenance in 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