WDR72, or WD repeat-containing protein 72, has been linked to multiple biological functions and disease conditions. It is crucial for intracellular vesicle trafficking, especially in ameloblasts where it may direct microtubule assembly for membrane mobilization and vesicle transport, playing a significant role in tooth enamel formation [1]. Mutations in WDR72 can lead to amelogenesis imperfecta, a dental enamel malformation, and are also associated with distal renal tubular acidosis [2,3].

In research, identification of biallelic WDR72 mutations in families with amelogenesis imperfecta has been achieved through whole exome sequence analyses. Some affected patients with these mutations also showed decreased serum pH, consistent with renal tubular acidosis diagnosis [3]. Additionally, in vitro experiments on ameloblast cell lines have shown that WDR72 regulates endocytosis of proteins, and its function is independent of intracellular vesicle acidification but impacts extracellular enamel matrix pH [1].

In conclusion, WDR72 is essential for proper tooth enamel formation through its role in vesicle trafficking in ameloblasts. Its mutations are associated with amelogenesis imperfecta and distal renal tubular acidosis. Studies on WDR72-related models contribute to understanding the mechanisms of these diseases, providing insights for potential diagnosis and treatment strategies.

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/