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Despite advances in targeted therapies, including proteasome inhibitors and the BCL\u20102 inhibitor venetoclax, drug resistance frequently occurs, with the underlying mechanisms poorly understood. This study investigates the role of lysosome\u2010associated protein transmembrane 5 (LAPTM5) in conferring resistance to venetoclax in relapsed MM. Using comprehensive analyses of publicly available databases and experimental validation, we demonstrated that LAPTM5 is upregulated and enhances autophagy in recurrent multiple myeloma cells, which is a key process for cell homeostasis and drug resistance. Mechanistic studies reveal that LAPTM5 facilitates autophagic flux, linking it to the cellular catabolic processes essential for survival under therapeutic stress. Our findings highlight the underexplored functions of LAPTM5 in modulating autophagy and drug resistance, we demonstrate that LAPTM5 confers resistance to venetoclax by enhancing autophagy, suggesting that targeting LAPTM5 may provide new avenues for overcoming treatment challenges. This research underscores the potential function of LAPTM5 as a therapeutic target in improving outcomes in MM treatment.<\/jats:p>","DOI":"10.1111\/jcmm.70331","type":"journal-article","created":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T22:39:59Z","timestamp":1735943999000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["<scp>LAPTM5<\/scp>\n                    Confers the Resistance to Venetoclax via Promoting the Autophagosome\u2010Lysosome Fusion in Multiple Myeloma"],"prefix":"10.1111","volume":"29","author":[{"given":"Yuxiang","family":"Li","sequence":"first","affiliation":[{"name":"School of Life Sciences Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Bai","sequence":"additional","affiliation":[{"name":"School of Life Sciences Anhui Medical University  Hefei 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