The lipid-lowering qualities of nicotinic acid, a B3 vitamin, have long been exploited to prevent cardiovascular disease and it’s associated mortality. Fifty years on from its arrival on the market, the receptors on which this drug acts upon have recently been identified as the ‘Nicotinic Acid Receptors’. A family of three highly homologous G-Protein Coupled Receptors (GPCRs), HM74, HM74A and GPR81 couple to the Gi class of G-proteins and are characterised by their differing affinities for nicotinic acid. HM74A has been identified as the high affinity receptor activated by μm concentrations; HM74A > HM74 > GPR81. HM74 and HM74A differ by only 15 base changes at the DNA sequence level, resulting in a shorter C-terminal tail in the HM74A receptor. Despite the widespread availability and clinical use of nicotinic acid, the clinical target and precise molecular mechanism by which nicotinic acid acts remains elusive. In this project, we have chosen to examine potential differences in the regulation of the high and low affinity receptors. C-terminal tail swaps, C-terminal truncations and site directed mutagenesis studies have been adopted to characterise desensitisation mechanisms.