P3h2, also known as Leprel1, is a prolyl 3-hydroxylase that catalyzes the post-translational formation of 3-hydroxyproline on collagens, mainly type IV [2,4]. It hydroxylates the 3' of prolines in collagen IV subchains in the endoplasmic reticulum, and is involved in pathways related to basement membrane regulation and angiogenesis [1,2]. It has overall biological importance in maintaining the integrity of basement membranes and new vessel formation. Genetic models, such as mouse models, are valuable for studying its functions.

In a P3h2ΔPod mouse line, the absence of P3H2 protein in podocytes induced a thin basement membrane nephropathy (TBMN) phenotype with a thinner glomerular basement membrane (GBM) than in WT mice, and over time, microhematuria and microalbuminuria developed. Mechanistically, differential quantitative proteomics of the GBM in these mice identified a significant decrease in the abundance of collagen IV subchains and their interaction partners, indicating that P3H2 is a regulator of the GBM and loss of it causes TBMN [1]. In another study, P3h2 knockdown in the model of laser-induced choroid neovascularization prevented pathological angiogenesis in vivo, showing that P3H2 is essential for angiogenesis properties of endothelial cells in vitro [2]. Also, in P3h2-null mice, almost every known site of prolyl 3-hydroxylation in types I and IV collagen from eye tissues was significantly under-hydroxylated compared with wild-type littermates, which may lead to progressive myopia [3].

In conclusion, P3h2 plays crucial roles in basement membrane regulation, angiogenesis, and collagen modification through its hydroxylation function on collagens. The study of P3h2 using KO/CKO mouse models has revealed its importance in diseases such as thin basement membrane nephropathy, high myopia, and pathological angiogenesis, providing insights into the underlying molecular mechanisms of these diseases.