MMP14 is a membrane-anchored endopeptidase that degrades extracellular matrix components, including collagen, elastin, and other structural proteins essential for tissue remodeling 12. The enzyme activates progelatinase A (MMP2), promoting cell growth and migration, and also regulates multiple signaling pathways by cleaving proteins such as DLL1 (inhibiting Notch signaling), GFRAL (suppressing GDF15-mediated aversive responses), and ADGRB1 (releasing vasculostatin-40 to inhibit angiogenesis). MMP14 is central to normal skeletal and extraskeletal tissue development; homozygous MMP14 mutations cause Winchester syndrome, a rare multisystem disorder characterized by craniofacial anomalies, reduced bone density, and dermal fibrosis due to defective collagen remodeling 3. In disease contexts, MMP14 is overexpressed in multiple malignancies including glioblastoma, colorectal cancer, and sarcomas, where it promotes metastasis and invasion 456. MMP14 also associates with cardiovascular pathology through elastin degradation 1 and has been linked to lipoedema through oestrogen-dependent mechanisms 7. Clinical development efforts targeting MMP14 include the small-molecule inhibitors CTS-1027 and rebimastat, though their clinical efficacy remains under investigation.