Importantly, as well as exploring how these affect activation of different G proteins at varying receptor expression levels, we also demonstrate the extent of constitutive activity of the long GPR35b isoform expressed endogenously in a pair of cell lines that are widely employed and well-studied as a cancer cell model (HT-29) and to explore compound toxicity in drug development (HEPG2) and to provide a model of the potential use of GPR35 agonists to limit fatty liver disease (31, 45, 51). Here, GPR35 is linked to fatty liver disease.