G protein-coupled receptors (GPCRs) and solute carrier transporters (SLCs) form the largest and the second-largest class of membrane protein in the human genome. GPCRs mediate cellular signaling and SLCs synergize with GPCR functions by regulating ligands and drugs availability to the receptors. Our goal is to determine the mechanisms at atomic resolution for their functions, using X-ray crystallography and cryoEM, assisted by molecular modeling, bioluminescence resonance energy transfer (BRET), cell signaling and molecular pharmacology assays. We sought to use our structural knowledge to develop innovative strategies with our academic and industrial partners for structure-based ligand design to better understand human health and disease.