The cellular trafficking of proteins in eukaryotic cells is a tightly regulated mechanism. The sorting nexin (SNX) proteins are established regulators of endosomal sorting and signalling, and have been identified as major actors of pathological states such as neurodegenerative diseases or even cancer and inflammation. The ability of their PX domain to bind to the phosphoinositides lipids contained in the membrane of different organelles is known to be a key factor that mediates the attachment on the cytoplasmic leaflets of the endosomal network. Using a combination of X-ray crystallography and Isothermal titration calorimetry, we aim to examine the interaction of SNX family members with biological regulators. The determination of the molecular structures of these proteins alone and in complex with these binding partners (and membrane phospholipids) will allow us to characterise the molecular basis of interactions. Based on our structural data, we will mutate residues of PX-domains located at the binding interface of the complexes in order to assess the relative contributions of these residues to complex formation. These mutants will then be used to address the function of PX-domain/protein complexes in cells. In the early stages of this work, we report the crystal and the SAXS solution structure of the domain-swapped Tetra-Trico-Peptide Repeat (TPR) domain of SNX21. This protein scaffold being known as a significant participant in many diverse processes including synaptic vesicle fusion and cargo transportation, and we intend to explore more about the function of the TPR-containing SNX proteins and their cellular binding partners and functions.