{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:34:51Z","timestamp":1787027691193,"version":"build-2736575974"},"reference-count":95,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,3]],"date-time":"2025-08-03T00:00:00Z","timestamp":1754179200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"State of Florida Board of Governors (GBF)"},{"name":"New Horizons in Alzheimer\u2019s Disease and Related Dementias (ADRD) program at Florida Atlantic University (HW)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The matrix metalloproteinase (MMP) family includes several membrane-bound enzymes. Membrane-type 5 matrix metalloproteinase (MT5-MMP) is unique amongst the MMP family in being primarily expressed in the brain and during development. It is proposed to contribute to synaptic plasticity and is implicated in several pathologies, including multiple cancers and Alzheimer\u2019s disease. In cancer, MT5-MMP expression has been correlated to cancer progression, but a distinct mechanistic role has yet to be uncovered. In Alzheimer\u2019s disease, MT5-MMP exhibits pro-amyloidogenic activity, functioning as an \u03b7-secretase that cleaves amyloid precursor protein (APP), ultimately generating two synaptotoxic fragments, A\u03b7-\u03b1 and A\u03b7-\u03b2. Several intracellular binding partners for MT5-MMP have been identified, and of these, N4BP2L1, EIG121, BIN1, or TMX3 binding to MT5-MMP results in a significant increase in MT5-MMP \u03b7-secretase activity. Beyond direct effects on APP, MT5-MMP may also facilitate APP trafficking to endosomal\/lysosomal compartments and enhance proinflammatory responses. Overall, the substrate profile of MT5-MMP has not been well defined, and selective inhibitors of MT5-MMP have not been described. These advances will be needed for further consideration of MT5-MMP as a therapeutic target in Alzheimer\u2019s disease and other pathologies.<\/jats:p>","DOI":"10.3390\/biom15081114","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T09:41:17Z","timestamp":1754300477000},"page":"1114","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Membrane-Type 5 Matrix Metalloproteinase (MT5-MMP): Background and Proposed Roles in Normal Physiology and Disease"],"prefix":"10.3390","volume":"15","author":[{"given":"Deepak","family":"Jadhav","sequence":"first","affiliation":[{"name":"Institute for Human Health & Disease Intervention (I-HEALTH) and Department of Chemistry & Biochemistry, Florida Atlantic University, Jupiter, FL 33458, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M.","family":"Knapinska","sequence":"additional","affiliation":[{"name":"Institute for Human Health & Disease Intervention (I-HEALTH) and Department of Chemistry & Biochemistry, Florida Atlantic University, Jupiter, FL 33458, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjie","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute for Human Health & Disease Intervention (I-HEALTH) and Department of Chemistry & Biochemistry, Florida Atlantic University, Jupiter, FL 33458, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7126-1601","authenticated-orcid":false,"given":"Gregg B.","family":"Fields","sequence":"additional","affiliation":[{"name":"Institute for Human Health & Disease Intervention (I-HEALTH) and Department of Chemistry & Biochemistry, Florida Atlantic University, Jupiter, FL 33458, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,3]]},"reference":[{"key":"ref_1","first-page":"2570","article-title":"Identification and characterization of human MT5-MMP, a new membrane-bound activator of progelatinase A overexpressed in brain tumors","volume":"59","author":"Llano","year":"1999","journal-title":"Cancer Res."},{"key":"ref_2","first-page":"555","article-title":"141. 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