This paper tells the story of G-protein coupled receptors, one of the most important scientific objects in contemporary biochemistry and molecular biology. By looking at how cell membrane receptors turned from a speculative concept into a central element in modern biochemistry over the past 40 years, we revisit the role of manipulability as a criterion for entity realism in wet-lab research. The central argument is that manipulability as a condition for reality becomes meaningful only once scientists have decided how to conceptually coordinate measurable effects distinctly to a specific object. We show that a scientific entity, such as GPCRs, is assigned varying degrees of reality throughout different stages of its discovery. The criteria of its reality, we further claim, cannot be made independently of the question about how this object becomes a standard by which the reality of neighbouring elements of enquiry is evaluated.