P3H4 (prolyl 3-hydroxylase family member 4) is part of a collagen-modifying enzyme complex that includes PLOD1 and P3H3, which catalyzes hydroxylation of lysine residues in collagen alpha chains and is required for normal collagen fibril assembly and cross-linking 1. This function is essential for maintaining normal bone density and skin stability through proper collagen processing 1. Despite being annotated as 'inactive,' P3H4 demonstrates increased thermal stability when treated with dextromethorphan, suggesting it retains enzymatic activity in collagen hyperhydroxylation 1. P3H4 has significant disease relevance in cancer, being upregulated in bladder cancer tissues where it associates with poor prognosis and shorter overall survival 234. The gene also shows overexpression in lung adenocarcinoma, correlating with decreased disease-free survival and overall survival 5. Functionally, P3H4 promotes cancer cell proliferation, migration, and invasion, with its knockdown inhibiting these oncogenic processes 45. Clinical significance includes its potential as a prognostic biomarker in multiple cancers and as a therapeutic target, with ETV4 acting as a transcriptional regulator of P3H4 expression 46.