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Recent research identifies myoferlin as a potential biomarker and a critical driver of cancer progression, particularly in breast cancer and pancreatic ductal adenocarcinoma. While its lack of specificity limits its use as a biomarker, its multifaceted role in cellular membrane dynamics makes it a promising therapeutic target. In cancer cells, myoferlin regulates the recycling and stability of receptor tyrosine kinases, thereby promoting invasion and metastasis. Beyond the plasma membrane, it maintains mitochondrial homeostasis by interacting with the machinery for mitochondrial fusion and calcium exchange at the endoplasmic reticulum\u2013mitochondria interface. Depletion of myoferlin disrupts these processes, leading to mitochondrial fragmentation, reduced ATP production, and iron-dependent cell death. Furthermore, myoferlin influences the tumour microenvironment by regulating pancreatic cancer-associated fibroblasts. It interacts with SEC24 to facilitate the coat protein complex II-mediated transport of the transforming growth factor-beta 1 receptor, driving the desmoplastic reaction and matrix protein deposition. The \u2018one punch\u2013two hits\u2019 strategy\u2014simultaneously targeting the metabolic and signalling pathways of both malignant cells and the stroma\u2014offers a novel therapeutic perspective. The development of small molecules targeting myoferlin\u2019s C2 domains confirms its potential to reduce tumour growth and metastatic dissemination.<\/jats:p>","DOI":"10.1042\/bst20260427","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:15:55Z","timestamp":1785410155000},"page":"985-992","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Myoferlin at the crossroad of vesicle trafficking and mitochondrial function: implications for pancreatic cancer progression and stromal reprogramming"],"prefix":"10.1042","volume":"54","author":[{"given":"Rapha\u00ebl","family":"Peiffer","sequence":"first","affiliation":[{"name":"2Personalized Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Laverdeur","sequence":"additional","affiliation":[{"name":"1Metastasis Research Laboratory, GIGA-Institute, University of Li\u00e8ge, Li\u00e8ge, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline","family":"Genbauffe","sequence":"additional","affiliation":[{"name":"1Metastasis Research Laboratory, GIGA-Institute, University of Li\u00e8ge, Li\u00e8ge, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akeila","family":"Bellahc\u00e8ne","sequence":"additional","affiliation":[{"name":"1Metastasis Research Laboratory, GIGA-Institute, University of Li\u00e8ge, Li\u00e8ge, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Rademaker","sequence":"additional","affiliation":[{"name":"1Metastasis Research Laboratory, GIGA-Institute, University of Li\u00e8ge, Li\u00e8ge, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6933-0134","authenticated-orcid":false,"given":"Olivier","family":"Peulen","sequence":"additional","affiliation":[{"name":"1Metastasis Research Laboratory, GIGA-Institute, University of Li\u00e8ge, Li\u00e8ge, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"2026073007155021400_B1","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1186\/1471-2148-10-231","article-title":"Phylogenetic analysis of ferlin genes reveals ancient eukaryotic origins","volume":"10","author":"Lek","year":"2010","journal-title":"BMC Evol. 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