Serpinh1, encoding a member of the serpin superfamily of serine proteinase inhibitors, is involved in the proper folding and secretion of collagen [5]. It is associated with multiple signaling pathways such as Wnt/β -catenin, PI3K -Akt, and has been linked to important biological processes including epithelial -to -mesenchymal transition (EMT), cell proliferation, apoptosis, and metastasis [1,3,4]. Genetic models like gene knockout (KO) mouse models can be valuable in studying its function.

In gastric cancer, SERPINH1 -silenced cells showed reduced survival, colony formation, migration, and invasion, suggesting it regulates EMT and GC progression via the Wnt/β -catenin pathway [1]. In prostate cancer, SERPINH1 bound to P62, reducing its ubiquitination degradation to promote bone metastasis [2]. In osteosarcoma, SERPINH1 promoted cell proliferation, migration, and invasion in vitro and in vivo by activating the PI3K -Akt signaling pathway [3]. In colorectal cancer, SERPINH1 overexpression enhanced cell proliferation, invasion, and migration, while knockdown had the opposite effects, with SERPINH1 accelerating G1/S phase cell cycle progression via the PI3K/Akt/mTOR pathway [4]. In hepatocellular carcinoma, knocking down SERPINH1 in cancer -associated fibroblasts led to a reduction in HCC cell proliferation, migration, and invasion [5].

In conclusion, Serpinh1 plays a crucial role in multiple biological processes, especially in the context of various cancers. The use of KO or conditional knockout (CKO) mouse models could potentially further elucidate its role in these disease conditions, highlighting its potential as a prognostic biomarker and therapeutic target in cancers such as gastric, prostate, osteosarcoma, colorectal, and hepatocellular carcinoma [1,2,3,4,5].