P3H1 (prolyl 3-hydroxylase 1) is a collagen-modifying enzyme that catalyzes the post-translational formation of 3-hydroxyproline in collagen sequences, particularly in types IV and V collagen 1. The protein functions as part of a ternary complex with CRTAP and PPIB in the endoplasmic reticulum, where these components form a bifunctional reaction center for coupled collagen processing 1. P3H1 contains a KDEL sequence essential for ER retention, and its removal leads to co-secretion with CRTAP 2. Mutations in P3H1 cause osteogenesis imperfecta type VIII, an autosomal recessive connective tissue disorder characterized by bone fragility and fractures 34. Recent studies have identified novel pathogenic variants, including dental anomalies not previously associated with P3H1 mutations 3. Beyond its established role in collagen metabolism, P3H1 has emerged as a cancer-related protein, showing significant overexpression across multiple tumor types and association with poor prognosis 56. In cancer contexts, P3H1 promotes malignant progression by enhancing cell proliferation, migration, and invasion, while also modulating the tumor immune microenvironment 7. The protein's dual roles in collagen processing and cancer progression make it both a critical factor in connective tissue disorders and a potential therapeutic target in oncology.