• SIRPα deficiency alters podocyte phosphoproteome, particularly affecting cytoskeleton-related processes and FAK phosphorylation at Y576.
• SIRPα regulates podocyte cytoskeleton rearrangement and migration via the Src/FAK/p38 MAPK signaling pathway.
• Urinary SIRPα and FAK levels are elevated in nephrotic syndrome patients and correlate with proteinuria, suggesting their potential as biomarkers.
• This is the first report linking increased urinary SIRPα to nephrotic syndrome, highlighting its clinical relevance.