The TIMP protein family: diverse roles in pathophysiology

The tissue inhibitors of matrix metalloproteinases (TIMPs) are a family of four matrisome proteins classically defined by their roles as the primary endogenous inhibitors of metalloproteinases (MPs). Their functions however are not limited to MP inhibition, with each family member harboring numerous MP-independent biological functions that play key roles in processes such as inflammation and apoptosis. Because of these multifaceted functions, TIMPs have been cited in diverse pathophysiological contexts. Herein, we provide a comprehensive overview of the MP-dependent and -independent roles of TIMPs across a range of pathological conditions. The potential therapeutic and biomarker applications of TIMPs in these disease contexts are also considered, highlighting the biomedical promise of this complex and often misunderstood protein family.