LIM-only (LMO) and LIM-homeodomain (LIM-HD) proteins play important roles in cell specification and cell development in many different tissues. Several members of this family also have causative roles in diseases including T-cell leukaemia and breast cancer, and are potential target for inhibitior development. These proteins share a common motif of two tandemly arrayed LIM domains at, or near, their C-termini, which mediate interactions with other proteins, including the LIM domain binding protein 1 (Ldb1). My laboratory has shown that a short intrinsically disordered peptide region in Ldb1, the LIM interaction domain (LID), binds in an extended fashion across the same face of both LIM domains, forming a tandem β-zipper interface in which short β-strands in the LID peptide augment β-hairpins in the LIM domains. We have now established that a number of other proteins use similar peptide regions to target the same binding face in the same manner - despite low sequence homology in the binding peptides. However, whereas all 4 LMO and 12 LIM-HD proteins (from mammals) bind Ldb1, these other binding peptides have higher levels of selectivity. We are investigating the basis for selectivity in this system and are using a range of protein engineering approaches to try and develop peptides with tailored binding properties for specific LIM targets.