P3h3, also known as Leprel2, is a member of the prolyl 3-hydroxylase (P3H) gene family. It is involved in collagen biosynthesis, specifically in the post-translational modification of collagen. Prolyl 3-hydroxylation is a crucial process for proper collagen structure and function, and P3h3 may play a role in lysine hydroxylation at specific cross-linking sites in collagen, which is important for the stability and integrity of the extracellular matrix [1,4,5].

P3h3-null mice phenocopy the collagen lysine under-hydroxylation and cross-linking abnormality similar to Ehlers-Danlos Syndrome Type VIA. This indicates that P3h3 is essential for normal collagen cross-linking in tissues like skin, bone, tendon, aorta, and cornea [1]. In lung cancer, P3h3 has tumor-suppressive activity. Ectopic expression of P3h3 inhibits cell proliferation, colony formation, migration, and invasion, while its knockdown leads to increased migratory and invasive potential [2]. In breast cancer, P3h3 expression is down-regulated by aberrant CpG methylation, and its methylation is associated with higher tumour grade [3].

In conclusion, P3h3 is vital for normal collagen post-translational modification and stability. Gene-knockout mouse models, such as the P3h3-null mice, have been instrumental in revealing its role in diseases like Ehlers-Danlos-related syndromes, as well as in cancer development, highlighting its potential as a therapeutic target in these disease areas [1,2,3].