PRSS23 (serine protease 23) is a trypsin-like serine protease with emerging roles in fibrotic and malignant diseases. Functionally, PRSS23 interacts with translation initiation factor eIF4E via its trypsin domain to modulate protein synthesis and oncogenic signaling 1. In normal physiology, PRSS23 is expressed in bone metabolism-related cells, including osteoblastic lineage cells in femoral head tissue 2, and participates in endothelial-to-mesenchymal transition during cardiac development 3. Pathologically, PRSS23 is significantly upregulated in gastric cancer tissues, where it activates the eIF4E-c-Myc axis to promote cell proliferation and correlates with lymph node metastasis and poor prognosis 14. In fibrotic diseases, PRSS23 marks a myofibroblast-like fibroblast subcluster in localized scleroderma and systemic sclerosis (SSc), where PRSS23/SFRP2+ fibroblast signatures correlate with progressive skin fibrosis 56. A PRSS23 antisense lncRNA (PRSS23-AS1) promotes breast cancer progression through the miR-3176/YBX1 axis 7. Additionally, PRSS23 expression is elevated in injured podocytes during IgA nephropathy with nephrotic syndrome 8. These findings establish PRSS23 as a versatile protease with therapeutic potential as a biomarker and drug target across multiple diseases.