LRRC17 (leucine-rich repeat containing 17) is a multifunctional regulator involved in bone homeostasis, cardiac function, and cellular senescence. In bone, LRRC17 acts as a negative regulator of osteoclast differentiation 1 and functions downstream of the Wnt/β-catenin pathway in BMSC osteogenic differentiation 2. LRRC17 controls BMSC senescence through mitophagy activation via the mTOR/PI3K pathway; knockdown rejuvenates aged mesenchymal stem cells and enhances their therapeutic efficacy in ovariectomy-induced osteoporosis 1. Beyond bone, LRRC17 regulates cardiac pathophysiology through a novel LRRc17-RANKL pathway that modulates mitophagy in atrial myocytes, with downregulation contributing to diabetic atrial remodeling and increased atrial fibrillation risk 3. In cardiac fibroblasts post-myocardial infarction, LRRC17 downregulation impairs ferroptosis regulation, promoting fibroblast migration and myocardial fibrosis 4. Additionally, LRRC17 serves as a cancer-associated fibroblast activation marker in colorectal cancer, with upregulation under TGF-β1 stimulation correlating with fibroblast activation and tumor progression 5. LRRC17 is also identified as a shared genetic factor in type 2 diabetes and osteoarthritis comorbidity 6, and as a diagnostic biomarker for idiopathic pulmonary fibrosis 7. These findings suggest LRRC17 is a potential therapeutic target for age-related bone disease, diabetic cardiac complications, fibrotic diseases, and psychiatric disorders 8.