l-Proline concentration is primarily related to the balance of enzymatic activities of proline dehydrogenase [proline oxidase (POX)] and Delta-1-pyrroline-5-carboxylate (P5C) reductase. As a result, P5C plays a pivotal role in maintaining the concentration of proline in body fluids and inborn errors of P5C metabolism lead to disturbance of proline metabolism. Several inborn errors of proline metabolism have been described. Hyperprolinemia type I (HPI) is a result of a deficiency in POX. The POX gene (PRODH) is located on chromosome 22 (22q11.2) and this region is deleted in velo-cardio-facial syndrome, a congenital malformation syndrome. In addition, this gene locus is related to susceptibility to schizophrenia. The other type of hyperprolinemia is HPII. It is caused by a deficiency in P5C dehydrogenase activity. Hypoprolinemia, on the other hand, is found in the recently described deficiency of P5C synthetase. This enzyme defect leads to hyperammonemia associated with hypoornithinemia, hypocitrullinemia, and hypoargininemia other than hypoprolinemia. Hyperhydroxyprolinemia is an autosomal recessive inheritance disorder caused by the deficiency of hydroxyproline oxidase. There are no symptoms and it is believed to be a benign metabolic disorder. The deficiency of ornithine aminotransferase causes transient hyperammonemia during early infancy due to deficiency of ornithine in the urea cycle. In later life, gyrate atrophy of the retina occurs due to hyperornithinemia, a paradoxical phenomenon. Finally, prolidase deficiency is a rare autosomal recessive hereditary disease. Prolidase catalyzes hydrolysis of dipeptide or oligopeptide with a C-terminal proline or hydroxyproline and its deficiency can cause mental retardation and severe skin ulcers.