Clathrin-mediated endocytosis (CME) plays a central role in fundamental processes such as synaptic vesicle recycling, receptor recycling, signalling and development. CME begins with clathrin assembly on the plasma membrane, facilitated by adaptor proteins. This process forms an endocytic vesicle that allows transport of cargo into the cell, and is followed by clathrin disassembly through the action of different adaptor/accessory proteins. A large number of different adaptor and accessory proteins are recruited during CME, in a spatially and temporally ordered manner. Although our understanding is growing as to the roles of individual adaptor proteins, we still do not understand the way in which some adaptors interact with clathrin or the molecular details of their interactions with one another in the presence of clathrin. Clathrin adaptor proteins contain short, linear clathrin-binding motifs, which form the basis of their interaction with the four distinct sites on the clathrin N-terminal domain (TD). An adaptor protein with tighter binding or more numerous clathrin binding sequences could displace one with weaker or fewer binding elements. This raises the question of whether adaptor proteins compete for binding to clathrin or whether they can bind simultaneously. Using certain biochemical and biophysical techniques in vitro and purified WT and mutant adaptor proteins, I have shown the complex ‘multiple TD linking effect’ of epsin 1 via the cooperative action of its two clathrin box motifs and unstructured region. Using the newly developed SPR/IAC (2-injection) method, I explored competition between five purified structurally and functionally diverse adaptor proteins when simultaneously binding to clathrin TD. I have shown how the complex structure of epsin 1 causes competition with β-arrestin 1 for clathrin TD binding. Such competition is observed between espin 1 and auxilin 1 as well, which reveals information about the mechanism of disassembly. However, β2-adaptin and auxilin 1 demonstrate no such competition.