Gene variants affecting members of the family of G-protein coupled receptors (GPCRs) have commonly been found to be associated with monogenic obesity. However, to determine whether these variants are pathogenic and thereby causal of obesity, functional analysis of the variant receptor is important. Advances in technology have made it easy and fast to predict pathogenicity of gene variants by use of computational models. However, the input of these technologies remains based on the knowledge gained from experimental approaches. As this knowledge is still rapidly expanding, novel gene variants are not always reliably characterized by in silico analyses. It is thus important to confirm the effects of variants through experimental studies in a cellular context. These types of experiment could also uncover beneficial effects of anti-obesity drugs on GPCRs whose function is affected by pathogenic DNA-variants. In the first part of this chapter, we will discuss the basis of cellular signalling pathways, specifically focussing on GPCRs. Next, we will provide an overview of state-of-the-art and well-established techniques to measure several components of these pathways, with reference to the melanocortin 4 receptor (MC4R) as an example since recent studies show that variants in this GPCR can modulate different aspects of its signalling pathway.