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Podocyte-specific reduction of both receptors in transgenic mice caused kidney disease characterised by albuminuria and glomerulosclerosis, with premature death occurring in some animals between 4 and 24 weeks. Receptor-deficient cultured podocytes exhibited &gt;50% cell loss within 7 days. Integrated proteomic and transcriptomic analyses revealed marked depletion of spliceosome-associated proteins and widespread intron retention with premature termination codons, indicating profound disruption of RNA processing. Phospho-proteomic profiling further showed that insulin\/IGF1 stimulation induces dynamic post-translational modifications across spliceosomal components and regulatory kinases. 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