Background: The cause and the mechanism for the development of systemic lupus erythematosus (SLE) are shrouded in mystery. The fact that tenascin-C (TN-C) is upregulated in response to trauma, inflammation, or cancer growth demonstrates that it is involved in cell signaling. Within the scope of this brief review, we discuss the significance of TN-C in the pathophysiology of SLE disease and the correlation between serum TN-C levels and disease activity. Objective: Analyzing the Role of Tenascin-C and Its Relationship to Disease Activity in SLE Methods: Tenascin-C, Systemic Lupus Erythematosus, and Disease Activity were all looked for in PubMed, Google Scholar, and Science Direct. References from relevant literature were also evaluated by the authors, but only the most recent or complete study from January 2000 to May 2021 was included. Due to the lack of sources for translation, documents in languages other than English have been ruled out. Papers that did not fall under the purview of major scientific investigations, such as unpublished manuscripts, oral presentations, conference abstracts, and dissertations, were omitted. Conclusion: Important novel biomarker for active SLE, TN-C is also a crucial molecule in tissue remodeling and is linked to SLE. There has to be more high-quality research done on TN-C before it can be recommended as a helpful blood biomarker for tracking disease activity and anticipating flares in SLE patients.