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LTBPs can also possess an LTBP-exclusive 4-cys domain near the N-terminus. The first 8-cys domain is known as the hybrid domain, since it shares similarities both with 8-cys and EGF-like motifs. Another hinge region is localized between the fourth 8-cys domain and the downstream EGF-like motif of LTBP-1. In addition to proteolytic processing, alternative splicing and usage of different promoters contribute to the structural variability of LTBPs (Figure 1). Three out of four LTBPs bind LAP, indicating that this interaction might have been the driving force for their co-evolution.