Alzheimer's disease (AD), the most common neurodegenerative disorder, affects millions of people worldwide. In a recent publication, Guo-Jun Chen and colleagues highlight the role of matrix metalloproteinase (MMP) 13 (also called Collagenase 3) in AD pathogenesis through regulating BACE1, a rate-limiting enzyme for β-amyloid (Aβ) peptide production. Proteolytic processing of amyloid precursor protein (APP) by BACE1 and γ-secretase generates Ab, which accumulate in brain senile plaques in AD. MMPs are a group of enzymes that degrade extracellular matrix and cleave proteins involved in signal transduction. MMPs have central roles in a myriad of biological processes including cancer invasion and neuroinflammation but their role in AD pathophysiology remains elusive. Initial reports highlighted the beneficial effects of MMP2 and MMP9 in attenuating Ab levels. Subsequent studies revealed that MT1-and MT5-MMP, two membrane-type MMPs, stimulate Ab production and AD pathogenesis and further, MT5-MMP5 releases a neurotoxic APP fragment that inhibits neuronal synaptic transmission. Previously, MMP13 was recognized for its role in extracellular matrix remodeling, bone and cartilage metabolism, as well as in tumor invasion and metastasis. Microglial cells were known to upregulate MMP13 in response to Ab, suggesting a likely involvement of this MMP in AD.