NPHS1 encodes nephrin, a critical cell adhesion molecule essential for glomerular filtration barrier integrity. Nephrin localizes to the podocyte slit diaphragm and anchors this structure to the actin cytoskeleton, regulating glomerular vascular permeability 1. Loss or dysfunction of nephrin architecture directly causes nephrotic syndrome through failure of the filtration barrier 2. Nephrin dysfunction contributes to nephrotic syndrome through multiple mechanisms. Genetic mutations in NPHS1 cause congenital and early-onset steroid-resistant nephrotic syndrome in children, with homozygous mutations demonstrating high penetrance 3. Additionally, circulating autoantibodies targeting nephrin have been identified in minimal change disease and post-transplant focal segmental glomerulosclerosis, where they induce nephrin phosphorylation and altered slit diaphragm localization, suggesting an autoimmune disease mechanism 24. Common NPHS1 genetic variants (rs437168) are associated with increased nephrotic syndrome susceptibility in pediatric populations and early-onset pre-eclampsia, likely through compromised glomerular function 56. Clinically, NPHS1 mutations account for severe childhood-onset nephrotic syndrome with progression to end-stage renal disease, while anti-nephrin antibodies represent emerging therapeutic targets for antibody-mediated disease subtypes, enabling precision medicine approaches in nephrotic syndrome management.