SERPINH1 (serpin family H member 1) is a collagen-binding chaperone protein with critical roles in collagen biosynthesis and tumor progression. In normal physiology, SERPINH1 functions as a molecular chaperone facilitating proper collagen folding and secretion in the endoplasmic reticulum 1. However, SERPINH1 is significantly upregulated across multiple cancer types, including glioblastoma 2, esophageal squamous cell carcinoma 3, lung adenocarcinoma 4, and laryngeal squamous cell carcinoma 5, where elevated expression correlates with poor prognosis. Mechanistically, SERPINH1 promotes cancer progression through distinct pathways: in lung adenocarcinoma, SERPINH1 stabilizes MMP-9 and activates TGF-β1 signaling in a positive feedback loop 4; in laryngeal cancer, it binds COL7A1 to enhance Wnt/β-catenin signaling 5; and in hepatocellular carcinoma, CAF-derived SERPINH1 activates SENP3/SP1/SQLE pathways 6. Beyond cancer, SERPINH1 is upregulated in diabetic retinopathy where miR-29b suppression of SERPINH1 reduces endothelial cell proliferation and migration 7. SERPINH1 is additionally identified as a key marker for epithelial-mesenchymal transition in esophageal cancer 3 and appears regulated by chr11 accessibility during ESCC metastasis 8. These findings position SERPINH1 as a promising therapeutic target across multiple malignancies.