Class A GPCRs, the so called “rhodopsin-like family” are by far the largest GPCR family, and are divided into several subgroups: aminergic, peptide, protein, lipid, melatonin, nucleotide, steroid, alicarboxylic acid, sensory, and orphan. They have a conventional transmembrane domain (TMD) that forms ligand-binding pocket and additional eight helices with a palmitoylated cysteine at the C terminal. The class A GPCRs transduce many important neural and endocrine signals. These receptors activate heterotrimeric G proteins and in many cases also cause activation of phospholipase D, an enzyme that can be controlled by the small G proteins ARF and RhoA.