The aim of this study was to evaluate the role of nephrotic syndrome 2 (NPHS2) gene polymorphism (R229Q) in chronic kidney disease which has unclear etiology. This study was conducted on 80 CKD patients compared with 40 age and sex matched normal volunteers acting as a control group. All of them underwent renal function tests and were assessed for the presence of NPHS2 gene polymorphism. We noticed that (R229Q) is a common variant in Egyptian population. Its concentration was (62.5%) in CKD patients and (55%) in control group. There was no significant difference with p-value > 0.05 between patients and control groups as regards to NPHS2 genotypes and alleles.