This proposed mechanism is supported by the protective effect of bortezomib in the PAN of R218Q KI mice, where an inhibition of the proteasomal proteases broke the pathogenic process, preserved nephrin protein homeostasis, and ameliorated the proteinuric podocytopathy, as well as the development of glomerulosclerosis. The gene discussed is NPHS1; the disease is glomerulosclerosis.