P3H2 (prolyl 3-hydroxylase 2) is an endoplasmic reticulum-localized enzyme that catalyzes the post-translational formation of 3-hydroxyproline residues in collagen chains 1. The enzyme demonstrates substrate specificity, showing high activity with type IV collagen (COL4A1) and lower activity with type I collagen (COL1A1), specifically hydroxylating the first proline in Gly-Pro-Hyp sequences where the third position contains 4-hydroxyproline 1. P3H2 plays critical roles in extracellular matrix stability and basement membrane integrity, with loss of function causing thin basement membrane nephropathy through reduced collagen IV abundance in the glomerular basement membrane 2. The enzyme is essential for angiogenesis, being induced by VEGF-A through p38 MAPK signaling and promoting pro-angiogenic endothelial cell behavior by modifying collagen IV architecture 3. Paradoxically, P3H2 exhibits context-dependent tumor suppressor properties, being epigenetically silenced in breast cancer where methylation is associated with estrogen receptor-positive tumors 4, yet promoting colorectal cancer metastasis through enhanced angiogenesis 5. P3H2 also contributes to tissue-specific collagen modification in fibrillar collagens, affecting sites beyond the primary Pro-986 position in types I, II, and V collagens 6.