Background: Among the various orphan G protein-coupled receptors, apelin receptor (APJ), originally identified in the
human genome as an orphan G-protein-coupled receptor, was deorphanised in 1998 with the discovery of its endogenous ligand, apelin. Apelin and APJ mRNA are widely expressed in peripheral tissues and the central nervous system in mammals.
Objective: In this review, we discuss the characteristics, pharmacology, physiology, and pathology of the apelin/APJ system in mammals.
Conclusion: Several physiological roles of the apelin/APJ system have been reported, including in homeostasis, cardiovascular
maintenance, angiogenesis, and neuroprotection. In cellular signaling, apelin has been shown to drive the PI3K/Akt, MAPK, and PKA
signaling pathways, leading to cell proliferation and protection from excitotoxicity. Apelin is also found in breast milk; therefore,
apelin is believed to contribute to the establishment of the infant immune system. Furthermore, activation of the apelin/APJ system is
reported to restore muscular weakness associated with aging. Thus, the apelin/APJ system represents a novel target for the prevention
of several important cardiovascular and neurodegenerative diseases and the maintenance of health during old age.