{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRPL35A encodes a ribosomal protein of the large 60S subunit that plays a crucial role in ribosome biogenesis by promoting the maturation of 28S and 5.8S ribosomal RNAs. Functional studies in Diamond‐Blackfan anemia (DBA) patients have shown that haploinsufficiency or deletion of RPL35A disrupts pre‐rRNA processing and impairs 60S subunit assembly, thereby contributing to the abnormal erythropoiesis and bone marrow failure characteristic of DBA. In these studies, both point mutations and large deletions—including those spanning 3q29—have been linked to a severe phenotype, with associated congenital malformations and a higher risk for treatment‐refractory anemia and additional cytopenias."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in ribosome assembly, RPL35A expression influences the cellular response to cytotoxic stress. Overexpression studies in Jurkat cells have demonstrated that elevated levels of RPL35A confer resistance to doxorubicin‐induced cell death, as well as to other apoptotic challenges. Moreover, in ovarian cancer models RPL35A is found to be abnormally upregulated, where it promotes tumor progression through modulation of transcription factor interactions (enhancing YY1/CTCF binding) and influencing pathways such as PPAR signaling. These findings implicate RPL35A not only in normal hematopoiesis but also in mechanisms that may underlie chemoresistance and aggressive cancer phenotypes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurther genomic surveys in diverse patient cohorts have reinforced the complex genetic landscape of DBA, noting that a substantial fraction of patients harbor copy number variations involving key ribosomal protein genes including RPL35A. Although one study in an Asian cohort focused primarily on mutational incidence and another report mentioned RPL35A in the context of cholangiocarcinoma without delineating its molecular role, these observations underscore the emerging significance of RPL35A alterations across different disease contexts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jason E Farrar, Michelle Nater, Emi Caywood, et al. 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