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This review focuses on the application of proteomic analysis in the identification of pathological conditions in a hospital setting, with a particular focus on the analysis of protein biomarkers. In particular, the main purpose of the review is to highlight the challenges associated with the identification of specific disease\u2010causing proteins, given their complex nature and the variety of posttranslational modifications (PTMs) they can undergo. PTMs, such as phosphorylation and glycosylation, play critical roles in protein function but can also lead to diseases if dysregulated. Proteomics plays an important role especially in various medical fields ranging from cardiology, internal medicine to hemato\u2010oncology emphasizing the interdisciplinary nature of this field. Traditional methods such as electrophoretic or immunochemical methods have been mainstay in protein detection; however, these techniques are limited in terms of specificity and sensitivity. Examples include the diagnosis of multiple myeloma and the detection of its specific protein or amyloidosis, which relies heavily on these conventional methods, which sometimes lead to false positives or inadequate disease monitoring. Mass spectrometry in this respect emerges as a superior alternative, providing high sensitivity and specificity in the detection and quantification of specific protein sequences. This technique is particularly beneficial for monitoring minimal residual disease (MRD) in the diagnosis of multiple myeloma where traditional methods fall short. Furthermore mass spectrometry can provide precise typing of amyloid proteins, which is crucial for the appropriate treatment of amyloidosis. This review summarizes the opportunities for proteomic determination using mass spectrometry between 2012 and 2024, highlighting the transformative potential of mass spectrometry in clinical proteomics and encouraging its wider use in diagnostic laboratories.<\/jats:p>","DOI":"10.1002\/jms.5116","type":"journal-article","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T03:13:48Z","timestamp":1739934828000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Mass Spectrometry\u2013Based Proteomics in Clinical Diagnosis of Amyloidosis and Multiple Myeloma: A Review (2012\u20132024)"],"prefix":"10.1002","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-0422-0068","authenticated-orcid":false,"given":"Katerina","family":"Kratka","sequence":"first","affiliation":[{"name":"Institute of Laboratory Medicine, Faculty of Medicine University of Ostrava  Ostrava Czech Republic"},{"name":"Institute of 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