SMOC2, also known as secreted modular calcium-binding protein 2, is a non-structural component of the extracellular matrix. It plays diverse roles in multiple biological processes. SMOC2 has been associated with pathways like TGF-β1/Smad3, BMP/TGF-β1, and integrin β3-FAK-paxillin, and is important in tissue remodeling, cell-matrix interactions, and cell behavior regulation [1,2,3,6]. Genetic models, such as knockout mouse models, are valuable for studying its functions.

In fibroblast-like synoviocytes of rheumatoid arthritis (RA), SMOC2 knockdown decreased cell migration and invasion by downregulating cytoskeleton-related genes, especially MYO1C, through transcriptional and post-transcriptional regulation [1]. In renal cell carcinoma, targeting SMOC2 by siRNA inhibited its induction of epithelial-to-mesenchymal transition (EMT), proliferation, and migration [2]. In heart failure models, SMOC2 knockdown improved cardiac function and inhibited the TGF-β1/Smad3 signaling-mediated autophagy [3]. In myocardial fibrosis, down-regulation of SMOC2 alleviated fibrosis by inhibiting the ILK/p38 pathway [4]. In nociceptive regulation, Smoc2 knockout in mice increased mechanical sensitivity and coupled activation of adjacent DRG neurons [5]. In abdominal aortic aneurysm, silence of SMOC2 inhibited vascular smooth muscle cell proliferation, migration, and extracellular matrix degradation [6].

In conclusion, SMOC2 is involved in a wide range of biological functions, including cell migration, invasion, proliferation, and tissue remodeling. Gene knockout mouse models have revealed its significance in diseases such as RA, renal cell carcinoma, heart failure, myocardial fibrosis, nociceptive regulation, and abdominal aortic aneurysm. Understanding SMOC2's functions provides potential therapeutic targets for these diseases.