Despite the role of renalase in regulating serum catecholamines and blood pressure, recent studies demonstrated that extra-renal renalase is also important. In renalase gene knocked-out mice, serum urea nitrogen, creatinine and aldosterone levels were unaffected, and cardiac systolic function was intact. However, mild ventricular hypertrophy was presented with decreased tolerance to ischemia, and increased risk of myocardial infarction, as much as 3 times higher than that of wild mice. Recombinant renalase replacement therapy could abort such abnormal changes [34] . Gu et al recently reported that renalase's expression is influenced by renal perfusion and abnormality of the renal perfusion is probably implicated in elevated serum catecholamine levels in cardiac failure [35] . Both renalase gene and protein are also observed in central and peripheral nerve systems [26] . Renalase is found in hypothalamus, pons, medulla oblongata and spinal cord, where the presympathetic and preganglionic neurons are located. It is highly plausible that renalase is also involved in regulating the central sympathetic output. Other extra-renal sources of renalase (i.e. skeletal muscles, small intestine and vasculature) are yet to be determined. The regulation of renalase's expression is another enigma that requires further studies. As of today, there have been some animal experiments that showed decreased renalase production associated with high intake of sodium and phosphate [36] . Renal denervation, a potential anti-hypertension treatment [37] , was reported to increase plasma renalase content and renalase expression in the kidneys in spontaneously hypertensive rats [38] . Data from clinical studies has shown that renalase level significantly decrease in patients with stroke and chronic kidney diseases, especially those on renal replacement therapy [39] [40] [41] , and is normalized in kidney and heart transplant recipients [42, 43] .