Cyp26b1, a member of the cytochrome P450 family, is responsible for the breakdown of retinoic acid. Appropriate levels of retinoic acid, regulated by Cyp26b1, are crucial for the normal development of multiple systems, including the cardiovascular, lymphatic, and skeletal systems, as well as in processes like keratinization, spermatogenesis, and lung development [1,2,3,4,5,6,7,8,9]. Genetic models, such as KO/CKO mouse models, can help reveal its functions in these processes.

In mouse models, genetic ablation of Cyp26b1 leads to abnormally thickened aortic valve leaflets and ventricular septal defects, indicating its role in heart valve morphogenesis [3]. Loss of Cyp26b1 in mice also results in a reduction of alveolar type 1 cells, failure of alveolar inflation, and early postnatal lethality, suggesting its importance in late gestational lung maturation [5]. In humans, pathogenic variants in CYP26B1 are associated with a wide range of phenotypes, from severe manifestations including skull anomalies, radio-humeral fusion, and oligodactyly to milder presentations such as craniosynostosis, hearing loss, and intellectual disability [4,7,8].

In conclusion, Cyp26b1 is an essential regulator in multiple biological processes. Studies using KO/CKO mouse models have revealed its crucial roles in heart valve and lung development. In humans, CYP26B1-related disorders span a broad phenotypic spectrum, highlighting the significance of this gene in normal development and the potential implications for understanding and treating related diseases.