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Osteoblast differentiation is a key process in bone homeostasis.Mutations in plastin 3 have been reported to be responsible for X-linked osteoporosis.Plastin 3 and plastin 2 act synergistically to regulate osteoblast differentiation.However,the bone-related function of plastin 1,another family member of plastins,has not been assessed.In this study,we addressed the functional importance of plastin 1 in osteoblasts.We characterized the expression pattes of plastin 1 during osteoblast differentiation and revealed its important role in this process.In both HEK 293T and hFOB1.19 cells,plastin 1 was demonstrated to regulate intracellular Ca2+.Accordingly,we revealed that higher Ca2+ concentration promotes osteoblast differentiation.Finally,we found that plastin 1 may play a compensatory role in osteoporosis patients with plastin 3 deficiency.Together,our results indicate that plastin 1 promotes osteoblast differentiation by regulating intracellular Ca2+.Our work sheds new light on the role played by plastins in bone homeostasis.