WDR72, or WD repeat-containing protein 72, is associated with several important biological functions. It has been implicated in intracellular vesicle trafficking, especially in ameloblasts, and may direct microtubule assembly for membrane mobilization and vesicle transport [1]. It is also related to acid-base homeostasis as mutations in WDR72 can cause distal renal tubular acidosis [2]. In addition, WDR72 is crucial in tooth enamel formation, with its deletion or mutation leading to amelogenesis imperfecta [1,3,4,5].

In studies, biallelic WDR72 mutations have been identified in families with amelogenesis imperfecta. Some affected patients also showed decreased serum pH, consistent with renal tubular acidosis [3]. In a novel in vitro ameloblast cell line and in vivo, WDR72 was shown to regulate endocytosis of proteins, and its function was independent of intracellular vesicle acidification but led to defective enamel matrix pH extracellularly [1].

In conclusion, WDR72 is essential for normal tooth enamel formation and maintaining acid-base balance. The discovery of its role in vesicle trafficking in ameloblasts through in vitro and in vivo studies provides a mechanistic basis for understanding physiologic and pathologic tissue mineralization. Mutations in WDR72 can lead to syndromic forms of amelogenesis imperfecta and distal renal tubular acidosis, highlighting its importance in these disease areas [1,2,3].

References:

1. Katsura, Kaitlin, Nakano, Yukiko, Zhang, Yan, Li, Wu, Den Besten, Pamela. 2022. WDR72 regulates vesicle trafficking in ameloblasts. In Scientific reports, 12, 2820. doi:10.1038/s41598-022-06751-1. https://pubmed.ncbi.nlm.nih.gov/35181734/

2. Wagner, Carsten A, Unwin, Robert, Lopez-Garcia, Sergio C, Bockenhauer, Detlef, Walsh, Stephen. 2023. The pathophysiology of distal renal tubular acidosis. In Nature reviews. Nephrology, 19, 384-400. doi:10.1038/s41581-023-00699-9. https://pubmed.ncbi.nlm.nih.gov/37016093/

3. Zhang, H, Koruyucu, M, Seymen, F, Simmer, J P, Hu, J C C. 2019. WDR72 Mutations Associated with Amelogenesis Imperfecta and Acidosis. In Journal of dental research, 98, 541-548. doi:10.1177/0022034518824571. https://pubmed.ncbi.nlm.nih.gov/30779877/

4. Kim, Youn Jung, Zhang, Hong, Lee, Yejin, Hu, Jan C-C, Kim, Jung-Wook. 2023. Novel WDR72 Mutations Causing Hypomaturation Amelogenesis Imperfecta. In Journal of personalized medicine, 13, . doi:10.3390/jpm13020326. https://pubmed.ncbi.nlm.nih.gov/36836560/

5. Martins, Daiana da Silva, Ionta, Franciny Querobim, Pompermaier Garlet, Gustavo, Rios, Daniela, Lussi, Adrian. 2024. Developmental Defects of Enamel. In Monographs in oral science, 32, 10-34. doi:10.1159/000538850. https://pubmed.ncbi.nlm.nih.gov/39321764/