Podocyte biology is a science promising a greater understanding of the mechanistic nature of proteinuria-related diseases. Injury to the podocytes and subsequent urinary excretion has a key role in glomerular disease pathogenesis and progression. Aim: To obtain an insight into the clinical significance of urinary mRNA profile of podocytes in proteinuric patients, we evaluated urinary messenger RNA (mRNA) expression of four podocyte proteins: alpha actin, synaptopodin, podocin, and podocalyxin, in glomerular insults of dif erent aetiologies: diabetes, HCV and immune disorders and correlated them with proteinuria and renal function. Methods: The study enrolled 80 proteinuric and non proteinuric Egyptian patients and 20 apparently healthy controls. Proteinuric patients (n=60) were divided into 3 groups according to etiology: HCV (n=20), nondiabetic (n=20) and diabetic (n=20) groups. In addition to a diabetic nonproteinuric group (n=20). Quantification of mRNA of synaptopodin, podocin, alpha actin and podocalyxin, in urinary sediment was performed by Real-Time PCR. Results: In the proteinuric HCV group the urinary mRNA levels of synaptopodin were significantly increased as compared to other diseased groups, Yet, no correlation was found between the urinary mRNA expression of the 4 podocyte proteins and HCV viral load. In the proteinuric nondiabetic group: Age and serum creatinine and synaptopodin mRNA expression were significantly lower than group in HCV proteinuric group. Alpha actin mRNA was significantly higher as compared to proteinuric diabetic patients. Yet Podocin mRNA was significantly lower than the proteinuric diabetic patients. Podocalyxin mRNA inversely correlated to alpha actin mRNA. In the proteinuric diabetic group: Proteinuria was significantly lower than both proteinuric HCV and proteinuric non- diabetic groups, and did not correlate to renal function or podocyte proteins. Urinary mRNA expression of alpha actin was significantly decreased as compared to control, proteinuric non diabetic and non- proteinuric diabetic groups. Also, the Podocin mRNA gene expression was significantly decreased when compared to proteinuric HCV and non- proteinuric diabetic.