LAUSR

Mutations in Plastin‐3 (PLS3) have been identified as a cause of X‐linked osteoporosis. To reveal the molecular mechanism of PLS3 on osteoporosis, we characterized the p.Ala253_Leu254insAsn mutation in PLS3. We first identified Lymphocyte cytosolic protein 1 (LCP1) as a binding partner of PLS3 and the mutation disrupted the interaction between them. We then confirmed the roles of PLS3 and LCP1 in the regulation of intracellular Ca2+, which was weakened by the mutant PLS3. Moreover, the interaction between PLS3 and LCP1 was enhanced under a low concentration of extracellular Ca2+. However, the mutation in PLS3 weakened the responsiveness. The reduced regulation on Ca2+ caused by p.Ala253_Leu254insAsn may be the possible molecular mechanism of osteoporosis.