TNS2 is a focal adhesion protein and tyrosine phosphatase that negatively regulates the PI3K-AKT signaling pathway, thereby controlling cell motility, proliferation, and insulin responsiveness 12. Its phosphatase activity depends on binding to phosphatidylinositol-3,4,5-triphosphate via the SH2 domain 3. In muscle under catabolic conditions, TNS2 dephosphorylates IRS1, promoting its degradation and muscle atrophy 23. In podocytes, TNS2 dephosphorylates nephrin (NPHS1), regulating mTORC1 activation; under high glucose conditions, TNS2 upregulation increases NPHS1 dephosphorylation, contributing to podocyte hypertrophy and proteinuria 4. TNS2 is critical for podocyte morphology, podocyte-glomerular basement membrane interactions, and glomerular filtration barrier integrity; TNS2 deficiency causes abnormal laminin accumulation, GBM thickening, and progressive glomerulosclerosis in a genetic background-dependent manner 567. Loss of TNS2 suppresses cell transformation through Akt inhibition; low TNS2 expression correlates with poor prognosis in breast and lung cancers 8. TNS2 variants are associated with preeclampsia and other hypertensive disorders of pregnancy, reflecting its role in blood pressure regulation and kidney function 9.