The human APJ receptor (APJR)， activated by apelin isoforms， regulates cardiovascular functions and fluid homeostasis. Understanding its structure-function relationship is crucial for a comprehensive knowledge of signalling aberrations that cause several physiological disorders. Here， we demonstrate the influence of extracellular loop (ECL) domains in the mechanism of β-arrestin-mediated signalling from human APJR: Apelin system. Alanine mutations of evolutionarily conserved residues were characterized using receptor internalization， β-arrestin pull-down， Akt phosphorylation and cell migration assay. C281A and KTL -AAA in ECL3 were deficient in all assays， whereas MDYS -AAAA mutant in ECL2 showed impaired β-arrestin-mediated signalling but demonstrated G -dependent cell migration. Our findings establish that conserved residues in the extracellular domain play a prominent role in modulating receptor interactions with the β-arrestin signalling cascade.