Recognizing the Molecular Multifunctionality and Interactome of TIMP-1

Tissue inhibitor of metalloproteinase 1 (TIMP-1) is a major player in preserving tissue integrity and has recently also emerged as a decisive factor in several human pathologies. This appreciation has prompted this review addressing the largely underestimated complexity of the functions executed by TIMP-1 and their mechanistic basis. In fact, the versatile impact of TIMP-1 on cellular functions stems from its two-domain structure harboring metalloproteinase-inhibitory and cytokine-like signaling activities. This feature leads to functional interactions with numerous and distinct enzymatic and cell-surface proteins that initiate an exceptionally broad range of downstream effects. We propose here that this multifunctionality and the remarkably large interactome explain the diverse biological consequences of TIMP-1 expression in health and disease.