biostudies-literatureXia LNatural Science Foundation of Anhui Province104007https://www.ebi.ac.uk/biostudies/studies/S-EPMC12907901biostudies-literatureUnknown91<h4>Background</h4>Multiple myeloma (MM) is an incurable plasma cell malignancy with high relapse rate. Recent studies have implicated dysregulated autophagy and ferroptosis in MM progression; however, the molecular links remain elusive. This study investigated the role of SDE2, a ubiquitin-like protein overexpressed in MM, in modulating autophagy-ferroptosis crosstalk via ATG5 degradation with the aim of identifying novel therapeutic targets.<h4>Methods</h4>Using bioinformatic analysis of TCGA data, we identified SDE2 as a prognostic marker in MM. Functional validation included Western blot, co-immunoprecipitation, and ubiquitination assays in MM cell lines (H929, RPMI8226, OPM-2, and KMS-11) and patient-derived samples. Transwell migration, soft agar colony formation, and flow cytometry Redox biologyInhibition of SDE2 promotes autophagy-dependent ferroptosis in multiple myeloma.PMC129079012023AH053319Zheng YXia LBao JChen XWWang XZhao YCfalseInhibition of SDE2 promotes autophagy-dependent ferroptosis in multiple myeloma.<h4>Background</h4>Multiple myeloma (MM) is an incurable plasma cell malignancy with high relapse rate. Recent studies have implicated dysregulated autophagy and ferroptosis in MM progression; however, the molecular links remain elusive. This study investigated the role of SDE2, a ubiquitin-like protein overexpressed in MM, in modulating autophagy-ferroptosis crosstalk via ATG5 degradation with the aim of identifying novel therapeutic targets.<h4>Methods</h4>Using bioinformatic analysis of TCGA data, we identified SDE2 as a prognostic marker in MM. Functional validation included Western blot, co-immunoprecipitation, and ubiquitination assays in MM cell lines (H929, RPMI8226, OPM-2, and KMS-11) and patient-derived samples. Transwell migration, soft agar colony formation, and flow cytometry 2026-01-01T00:00:00Z2026 Jan2026-07-16T05:11:53.353Z2026-07-09T10:36:46.293ZS-EPMC129079014166667610.1016/j.redox.2026.104007