Regulated endocrine-specific protein-18 (RESP18), a novel 18-kDa protein, was first identified in neuroendocrine tissue. Subsequent studies showed that Resp18 is expressed in the adrenal medulla, brain, pancreas, pituitary, retina, stomach, superior cervical ganglion, testis, and thyroid and also circulates in the plasma. Resp18 has partial homology with the islet cell antigen 512, also known as protein tyrosine phosphatase, receptor type N (PTPRN), but does not have phosphatase activity. Resp18 might serve as an intracellular signal; however, its function is unclear. It is regulated by dopamine, glucocorticoids, and insulin. We recently reported that the targeted disruption of the Resp18 locus in Dahl salt-sensitive rats increased their blood pressure and caused renal injury. The aim of the present review was to provide a comprehensive summary of the reported data currently available, especially the expression and proposed organ-specific function of Resp18.