OSGEP (O-sialoglycoprotein endopeptidase) is a catalytic component of the EKC/KEOPS complex that catalyzes the formation of N6-threonylcarbamoyladenosine (t6A37), a critical tRNA modification at position 37 of tRNAs reading adenine-starting codons 1. This modification ensures translational fidelity by enabling accurate decoding of ANN codons (A followed by any nucleotide) 2. OSGEP functions in the cytoplasm and nucleus across multiple tissues 3, with ubiquitous expression suggesting broad biological roles. Mechanistically, OSGEP regulates protein translation quality and endoplasmic reticulum (ER) homeostasis. In pancreatic β-cells, OSGEP maintains proinsulin translation fidelity; its loss impairs protein synthesis, activates the unfolded protein response, and triggers apoptosis 1. Beyond translation, OSGEP functions as a ferroptosis suppressor by modulating m6A methylation of GPX4 mRNA, protecting against cerebral ischemia-reperfusion injury 4. Clinically, OSGEP mutations cause Galloway-Mowat syndrome 3 (GAMOS), an autosomal-recessive disorder combining early-onset steroid-resistant nephrotic syndrome with primary microcephaly, brain atrophy, and developmental delay 5. OSGEP mutations typically cause earlier disease onset and shorter survival than WDR73 mutations 6. Additionally, OSGEP loss in melanoma disrupts translational control, triggering RIG-I-mediated anti-tumor immunity 2. OSGEP overexpression improves insulin secretion in high-fat diet models, positioning it as a potential diabetes therapeutic target 1.