The rules that govern the folding of membrane proteins are still not completely understood when compared with the well-detailed set of principles described for the folding of soluble proteins. Although the molecular determinants of the folding mechanism should be basically the same for both types of proteins, the main difference, which in turn could also represent the main difficulty, is the media that surrounds the protein. In this sense, it would be useful to develop new molecular techniques that allow for the study of the folding mechanism of membrane proteins in their natural media, the membrane. In the present work we have collected a series of studies devoted to understanding the principles that govern the molecular mechanism of folding and packing of membrane proteins, an important group of the proteome. In particular, we have focused our attention on Glycophorin A (GpA), a single span membrane protein, which has been extensively used as a model system to study helix-helix transmembrane (TM) packing. Here, we report on the importance of the molecular distance between the critical oligomerisation motif and polar residues in TM fragments. We have also given an account of the influence of the length of the TM fragment as well as the effect of proline residues on the packing of TM alpha helices.