RNFT1 is an E3 ubiquitin-protein ligase localized to the endoplasmic reticulum (ER) that functions in ER-associated degradation (ERAD), targeting misfolded proteins for proteasome-mediated degradation 1. The protein possesses a RING-finger motif and transmembrane domain characteristic of ERAD E3 ligases, and its expression is significantly upregulated by ER stress 1. RNFT1 exhibits E3 autoubiquitination activity and confers resistance to ER stressors in an E3-activity-dependent manner 1, protecting cells from ER stress-induced apoptosis. In cancer biology, RNFT1 suppresses breast cancer metastasis by catalyzing K63 polyubiquitination of PDCD10, promoting its p62-selective autophagic degradation and enhancing cell adhesion and contractility 23. Beyond its canonical ERAD function, RNFT1 has been identified as a prognostic factor in hepatocellular carcinoma 4 and pediatric acute myeloid leukemia 5, suggesting broader roles in cancer biology. Clinically, RNFT1 represents a potential therapeutic target for metastatic breast cancer and may inform prognostic stratification in hematologic malignancies, though its expression appears downregulated during Mycobacterium tuberculosis infection 6.