NPNT (nephronectin) is an extracellular matrix protein that functions as a ligand for integrin α8β1 and plays crucial roles in tissue development and homeostasis 1. The protein contains EGF-like repeat domains, a MAM domain, RGD motif, and coiled-coil domain, mediating integrin-based signaling pathways 2. In kidney development, NPNT regulates GDNF expression through integrin α8β1 interaction, essential for proper renal morphogenesis 3. The protein exhibits tissue-specific functions, including regulation of aldosterone production in adrenal zona glomerulosa through Wnt pathway signaling 4. NPNT is critically involved in skeletal muscle homeostasis, where its expression is regulated by METTL3-mediated m6A modifications, and deficiency contributes to aging-associated muscle degeneration 5. In pulmonary pathology, NPNT acts as an antiaging molecule that inhibits cellular senescence through the ITGA3/YAP1 signaling axis, with reduced expression correlating with idiopathic pulmonary fibrosis severity 6. Disease relevance includes associations with COPD progression, where miR-378 targets NPNT 7, and Alzheimer's disease, where NPNT emerges as a top differentially expressed gene 8. Clinically, NPNT represents a potential therapeutic target for tissue regeneration, bone diseases, and age-related pathologies 2.