{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nWDR72 is emerging as a multifunctional protein with a well‐documented role in dental enamel formation. Studies in families with autosomal recessive hypomaturation amelogenesis imperfecta have revealed that mutations in WDR72 lead to poorly mineralized, discolored enamel with early attrition and the retention of enamel matrix proteins. Structural predictions indicate that WDR72 contains beta‐propeller folds and an α‐solenoid tail—features characteristic of vesicle coat proteins—and experimental evidence demonstrates its intracellular, predominantly Golgi‐associated localization. These observations support a model in which WDR72 acts as a scaffold for protein–protein interactions that are essential for the regulation of vesicle trafficking and endocytic removal of amelogenin fragments during the enamel maturation stage."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in odontogenesis, genetic analyses have implicated WDR72 in renal function. Genome‐wide association studies have associated WDR72 with loci that may influence creatinine production and secretion, and additional reports have identified pathogenic mutations in WDR72 in patients with hereditary distal renal tubular acidosis. These findings suggest that WDR72 is necessary for proper kidney tubular acid–base homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent investigations further indicate that WDR72 may have broader roles in tissue differentiation. In periodontal ligament stem cells, for example, WDR72 has been shown to be crucial for osteogenic differentiation. The protein’s structural features—notably the C‐terminal CAAX motif that facilitates its recruitment to the Golgi—are critical for its function in vesicular trafficking, a process that appears to be central not only to enamel biomineralization but also to other differentiation and secretion pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Walid El-Sayed, David A Parry, Roger C Shore, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in the beta propeller WDR72 cause autosomal-recessive hypomaturation amelogenesis imperfecta."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2009.09.014"}], "href": "https://doi.org/10.1016/j.ajhg.2009.09.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19853237"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19853237"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "S-K Lee, F Seymen, K-E Lee, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "WDR72 models of structure and function: a stage-specific regulator of enamel mineralization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Matrix Biol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.matbio.2014.06.005"}], "href": "https://doi.org/10.1016/j.matbio.2014.06.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25008349"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25008349"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Julia Hentschel, Dana Tatun, Dmitri Parkhomchuk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of the first multi-exonic WDR72 deletion in isolated amelogenesis imperfecta, and generation of a WDR72-specific copy number screening tool."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2016.05.040"}], "href": "https://doi.org/10.1016/j.gene.2016.05.040"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27259663"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27259663"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "H Zhang, M Koruyucu, F Seymen, et al. 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