Renal diseases, including glomerulonephritis, acute kidney injury, chronic kidney failure, and kidney tumors are all current global health challenges. Lesions in other systems can cause renal diseases and can affect other systems or even the whole body. Despite ongoing advancements in pharmaceutical and technological innovations, the prognosis for end-stage renal disease, encompassing renal failure and tumors, continues to be bleak. Follistatin-like protein 1 (FSTL1) is a secreted glycoprotein produced mainly by mesenchymal cells. FSTL1 is a glycoprotein that belongs to the family of secreted, cysteine-rich acidic proteins (SPARC). It plays a pivotal role in cell survival, proliferation, differentiation, and migration, as well as in modulating inflammation and immune responses. Research has shown that FSTL1 plays a crucial role in the onset and progression of renal diseases. This review explores the functions and underlying mechanisms of FSTL1 in kidney pathology. SIGNIFICANCE STATEMENT: This review highlights the pivotal role of FSTL1 in renal diseases, particularly its involvement in renal fibrosis, inflammation, and ischemia-reperfusion injury. By elucidating its dual roles across different pathologies, this work underscores FSTL1's potential as both a biomarker and a therapeutic target, offering novel insights for managing chronic kidney disease and associated complications.Copyright © 2025 American Society for Pharmacology and Experimental Therapeutics. Published by Elsevier Inc. All rights reserved.