Abstract: SERPINA3/Serpina3c is a serine (or cysteine) peptidase inhibitor that inhibits cathepsin G and exerts anti-inflammatory effects.At present, most of the understanding of the functions of SERPINA3/Serpina3c comes from studies in the context of carcinogenesis. SERPINA3/Serpina3c is involved in various cellular biological processes such as gene expression, cell cycle progression, apoptosis, signal transduction, and carcinogenesis. In recent years, the study on SERPINA3/Serpina3c in non-tumor diseases is increasing. This article systematically analyzes the research hotspots and trends of SERPINA3/Serpina3c, reviews its regulatory mechanisms on the cell signaling axis in non-tumor diseases, and provides some ideas for the molecular mechanism research of SERPINA3/Serpina3c in non-tumor diseases.