SYNPO encodes synaptopodin, an actin-binding protein critical for maintaining podocyte structure and function in the kidney. SYNPO localizes to podocyte foot processes and dendritic spine apparatuses, where it regulates actin cytoskeleton organization and bundle assembly 1. In podocytes, SYNPO is essential for foot process architecture and integrity; its absence exacerbates disease progression in Alport syndrome by impairing myosin IIA localization to actin cables near the glomerular basement membrane, facilitating podocyte detachment 1. SYNPO stability is regulated by Flotillin-2, which protects synaptopodin from proteasomal degradation; loss of this protection contributes to podocyte injury in diabetic nephropathy 2. Additionally, SYNPO expression is downregulated in focal segmental glomerulosclerosis (FSGS) associated with TRPC6 mutations, correlating with F-actin cytoskeleton disruption 3. Beyond kidney function, SYNPO plays a protective role in intestinal epithelial barrier maintenance, where microbiota-derived butyrate selectively induces SYNPO expression at tight junctions; SYNPO-deficient mice show exacerbated colitis susceptibility 4. Recent evidence suggests SYNPO also functions in immune regulation, with its upregulation in calcium signaling pathways promoting neutrophil activation in cancer microenvironments 5. SYNPO represents a therapeutic target in glomerular and gastrointestinal diseases through actin cytoskeleton stabilization.