In eukaryotic cells, each transport vesicle that buds from a compartment must be selectively delivered to a target compartment. This selectivity depends on numerous factors that coordinate the initial docking and fusion of the incoming vesicle with the target membrane. Some pathological conditions including neurological and developmental disorders are due to aberrant protein localization originated by malfunction of the corresponding sorting machinery. In this seminar we will present the X-ray crystallography platform at CIC bioGUNE and examples of combined structural and cellular analyses of two multiportein complexes, GARP and Retromer, implicated in retrograde transport. Defects in these complexes have been associated with Amyotrophic Lateral Sclerosis, Parkinson’s and Alzheimer’s disease.