 This study examined the signaling bias of angiotensin-2 on II, analog sarcosine-1-l4-l8, SiI, and found that despite being unable to activate G-protein signaling, SiI was able to induce cellular signaling outcomes through beta-restin-2-dependent mechanisms. The study also showed that overexpression of the angiotensin-2-type-1 receptor, at 1R, led to a misrepresentation of the signaling bias of SiI, as it appeared to be a partial agonist for G-protein signaling and lacked beta-restin-exclusive functional specificity. This study suggests that overexpression of at 1R can lead to misleading conclusions about the signaling bias of GPCR ligands in physiologically relevant contexts. This article was authored by Angus Lee, Samuel Liu, Renika Huang, and others.