P4hb, also known as prolyl 4-hydroxylase subunit beta, is an endoplasmic reticulum molecular chaperone protein with oxidoreductase, chaperone and isomerase activities. It can catalyze the formation, breakage and rearrangement of disulfide bonds through two thioredoxin domains, which is crucial for maintaining the oxidizing environment in the endoplasmic reticulum [3,4,5].

In esophageal cancer, ESCC-derived extracellular vesicles containing P4HB can induce apoptosis of skeletal muscle cells, promoting muscle wasting via regulating the PHGDH/Bcl-2/caspase-3 pathway, and the P4HB inhibitor CCF642 can prevent muscle wasting in a mouse model [1]. In HepG2 cells, defective P4HB UFMylation promotes P4HB protein degradation via the ubiquitin-proteasome pathway, causing mitochondrial function damage, oxidative stress, and endoplasmic reticulum stress [2]. High P4HB expression is significantly correlated with shorter overall survival in various cancers, and in bladder carcinoma, it can serve as a diagnostic and prognostic biomarker, being involved in protein processing in the endoplasmic reticulum [4,5]. In glioblastoma stem cells, transcriptional silencing of P4HB induces apoptosis and reduces stem-like characteristics, and treatment with CCF624 or securinine prolongs survival in mouse models [6]. In malignant glioma, P4HB expression is associated with temozolomide response and prognosis, and can be used as an independent prognostic indicator, especially in high-grade gliomas [7].

In conclusion, P4HB is essential for maintaining endoplasmic reticulum function and has a significant impact on various biological processes and disease conditions. Mouse models, such as the ESCC-induced cachexia mouse model and patient-derived xenograft mouse models in glioblastoma, have been crucial in revealing P4HB's role in cancer-related muscle wasting, cancer prognosis, and stem cell-related processes, providing potential targets for treating these diseases.