Kidney disease is a kidney injury or disease that affects many people globally. The study aims to evaluate the effect of Phosphatidyl Inositol (4,5) Bisphosphate, 5-Phosphatase (PIP2) enzyme on calcium (Ca²⁺) levels and its relationship to oculocerebrorenal gene variations in kidney stone and kidney failure patients. The enzyme-produced amount was measured by enzyme-linked immunosorbent assay (ELISA). Genetic variations were studied through the polymerase chain reaction (PCR) technique, followed by the sequencing of fragments of the exons (9, 13, 15). Blood samples were collected from eighty patients (40 with kidney stones and 40 with kidney failure), and 40 were healthy individuals. Results showed a significant difference between the levels of PIP2 in patients with kidney stones (6.63±0.22) and kidney failure patients (9.13±0.27), at a p-value of 0.004, compared with the control group (1.87±0.14), at a p-value of 0.02. Also, the differences in the serum Ca²⁺ levels were highly significant differences (9.55±0.25, 8.19±0.17) and the control group (9.46±0.04) at p-values of 0.004 and 0.001, respectively. In addition to the results of urea, creatinine, and uric acid, there were highly significant differences between kidney failure 140.35±6.55, 8.69±0.50, and 8.42±0.23 versus the control group 27.07±1.13, 0.69±0.04, and 4.53±0.14, respectively. The p-value was 0.001. In patients with kidney stones, the uric acid level was significant at 6.30±0.21, with a p-value of 0.001. Sequencing revealed a variant A/G in exon 15 in a female patient suffering from kidney failure and two intronic substitutions (c.1359+262G>A) and (c.1359+251G>C) before exon 13 in a 55-year-old male patient with kidney failure.