Cyp27b1, also known as 1α-hydroxylase, is a key enzyme in vitamin D metabolism. It converts 25-hydroxyvitamin D (25OHD) into the active form 1,25-dihydroxyvitamin D (1,25(OH)2D), which is crucial for regulating calcium and phosphate homeostasis, and also plays roles in the innate and adaptive immune responses, cell proliferation, differentiation, and apoptosis [1,4,5,6]. The gene is involved in the vitamin D metabolic pathway, and its function is essential for normal skeletal development and overall health. Genetic models, such as knockout (KO) mouse models, have been valuable for studying its role in vivo.

In KO mouse models, deletion of both submodules related to Cyp27b1 expression in the kidney fully eliminates basal Cyp27b1 expression, leading to a systemic and skeletal phenotype similar to that of the Cyp27b1-KO mouse due to depletion of 1,25(OH)2D3 and high parathyroid hormone (PTH) levels. This indicates the critical role of Cyp27b1 in maintaining normal calcium and phosphate regulation and skeletal health [5]. Additionally, in human studies, polymorphisms in the CYP27B1 gene, like rs10877012, are associated with the risk of developing colorectal cancer, with the T allele at the polymorphic site being associated with a decreased CRC incidence [3]. Also, SNPs in CYP27B1, along with other genes in the vitamin D pathway, are associated with overall survival and progression-free survival in non-small cell lung cancer patients [2].

In conclusion, Cyp27b1 is essential for vitamin D activation and the regulation of calcium and phosphate metabolism, with implications for skeletal health. Studies using KO mouse models and human genetic association studies have revealed its role in diseases such as colorectal cancer and non-small cell lung cancer. Understanding Cyp27b1's function provides insights into the mechanisms of these diseases and may offer potential targets for therapeutic intervention.