P4HA2 encodes prolyl 4-hydroxylase subunit alpha 2, which catalyzes the post-translational formation of 4-hydroxyproline in collagen sequences and functions within the endoplasmic reticulum 1. Beyond its classical collagen modification role, P4HA2 exhibits diverse pathological functions across multiple diseases. In hepatic cholestatic diseases, P4HA2 is highly elevated in patients with primary biliary cholangitis and primary sclerosing cholangitis, where it promotes ductular reaction and biliary fibrosis by regulating the SAV1-mediated Hippo signaling pathway 2. In cancer, P4HA2 demonstrates oncogenic properties through multiple mechanisms: it directly binds and hydroxylates mTOR at proline 2341, activating mTOR kinase and downstream effectors like S6K and AKT in lung adenocarcinoma 3; it promotes radiotherapy resistance in breast cancer by enhancing stemness and DNA damage repair 4; and it mediates resistance to iodine-125 brachytherapy in esophageal cancer through PINK1/parkin-dependent mitophagy 5. P4HA2 also regulates glycolysis-driven histone lactylation in gastric cancer 6. Clinically, P4HA2 mutations are associated with early-onset high myopia 7, while its overexpression correlates with poor prognosis in multiple cancers 8. These findings establish P4HA2 as a potential therapeutic target across diverse pathological conditions.