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Due to its intricate molecular mechanisms and diverse organ involvement, the disease poses significant diagnostic and therapeutic challenges. This review explores the molecular landscape of AL amyloidosis, emphasizing genetic, transcriptomic and proteomic alterations. Key findings include chromosomal abnormalities, somatic mutations, aberrant gene expression, disrupted protein folding pathways and the role of cytokine and chemokine secretion. These factors collectively drive the overproduction and destabilization of amyloidogenic LCs, leading to organ\u2010specific amyloid deposition, clinical heterogeneity and variable patient outcomes. Despite therapeutic advancements, the disease's complexity challenges the development of effective biological models. Progressing towards personalized therapies requires the development of preclinical models and the identification of biomarkers and molecular data to design targeted interventions. This review highlights the importance of integrating DNA, RNA and protein\u2010level analyses to deepen the understanding of AL amyloidosis pathogenesis. Such insights are pivotal for improving diagnostics, prognostics and therapeutic strategies, ultimately advancing precision medicine for this challenging disease.<\/jats:p>","DOI":"10.1111\/bjh.20070","type":"journal-article","created":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T03:20:08Z","timestamp":1744341608000},"page":"1297-1311","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The molecular landscape of\n                    <scp>AL<\/scp>\n                    amyloidosis"],"prefix":"10.1111","volume":"206","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8641-7813","authenticated-orcid":false,"given":"Tal","family":"Zvida\u2010Bloch","sequence":"first","affiliation":[{"name":"Department of Molecular Biology, Faculty of Natural Sciences Ariel University  Ariel Israel"},{"name":"Translational Research Lab Assuta Medical Centers  Tel\u2010Aviv 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