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Although accumulating evidence suggests that defective ribosome biogenesis leads to p53\u2010mediated apoptosis in erythroid progenitor cells, little is known regarding the underlying causes of the physical abnormalities. In this study, we established induced pluripotent stem cells from a DBA patient with <jats:italic>RPL5<\/jats:italic> haploinsufficiency. These cells retained the ability to differentiate into osteoblasts and chondrocytes. However, <jats:italic>RPL5<\/jats:italic> haploinsufficiency impaired the production of mucins and increased apoptosis in differentiated chondrocytes. Increased expression of the pro\u2010apoptotic genes <jats:italic>BAX<\/jats:italic> and <jats:italic>CASP9<\/jats:italic> further indicated that <jats:italic>RPL5<\/jats:italic> haploinsufficiency triggered p53\u2010mediated apoptosis in chondrocytes. Murine double minute 2 (MDM2), the primary negative regulator of p53, plays a crucial role in erythroid aplasia in DBA patient. We found the phosphorylation level of MDM2 was significantly decreased in <jats:italic>RPL5<\/jats:italic> haploinsufficient chondrocytes. In stark contrast, we found no evidence that <jats:italic>RPL5<\/jats:italic> haploinsufficiency impaired osteogenesis. Collectively, our data support a model in which <jats:italic>RPL5<\/jats:italic> haploinsufficiency specifically induces p53\u2010mediated apoptosis in chondrocytes through MDM2 inhibition, which leads to physical abnormalities in DBA patients.<\/jats:p>","DOI":"10.1111\/pin.13168","type":"journal-article","created":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T04:26:43Z","timestamp":1632976003000},"page":"803-813","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Investigation of the molecular causes underlying physical abnormalities in Diamond\u2010Blackfan anemia patients with <i>RPL5<\/i> haploinsufficiency"],"prefix":"10.1111","volume":"71","author":[{"given":"Yuko","family":"Fukui","sequence":"first","affiliation":[{"name":"Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama University  Okayama 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