P3H2, also known as Leprel1, is a prolyl 3-hydroxylase enzyme that catalyzes the post-translational formation of 3-hydroxyproline on collagens, mainly type IV [2,4]. It is involved in the VEGF-A/VEGFR-2 signaling pathway through p38 MAPK and plays a crucial role in angiogenesis [2]. It also has implications in basement membrane regulation, which is important for maintaining normal physiological functions [1,3]. Genetic models, such as knockout mice, have been valuable in studying its functions.

In P3h2ΔPod mice, the absence of P3H2 in podocytes leads to thin basement membrane nephropathy with a thinner glomerular basement membrane, microhematuria, and microalbuminuria over time. Differential quantitative proteomics showed a decrease in the abundance of collagen IV subchains and their interaction partners [3]. P3H2-null mice are embryonic-lethal by embryonic day 8.5 due to the interaction of non-3-hydroxylated embryonic type IV collagen with maternal platelet-specific glycoprotein VI, resulting in maternal platelet aggregation and embryo death. This phenotype is rescued in P3H2 and GPVI double null mice [5]. In addition, P3h2-null mice have significantly under-hydroxylated collagens in eye tissues, which may lead to structural abnormalities in the sclera and progressive myopia [6].

In conclusion, P3H2 is essential for the proper hydroxylation of collagen IV, which is crucial for angiogenesis, basement membrane regulation, and normal development. The study of P3H2 knockout mouse models has revealed its roles in diseases such as thin basement membrane nephropathy, embryonic lethality related to platelet aggregation, and myopia. These findings provide important insights into the biological functions of P3H2 and its implications in various disease conditions.