MRPS28 encodes a small mitochondrial ribosomal subunit protein (bS1m) essential for mitochondrial protein synthesis. The protein functions as a structural component of the mitochondrial small ribosomal subunit (mtSSU) 1, where it participates in the translation of the 13 mtDNA-encoded polypeptides required for oxidative phosphorylation (OXPHOS) complex biogenesis 1. Mutations in MRPS28 impair mtSSU assembly and mitochondrial translation, consequently compromising OXPHOS biogenesis and cellular respiration 1. Pathogenic variants cause Combined Oxidative Phosphorylation Deficiency 47, presenting with intrauterine growth retardation, craniofacial dysmorphism, and developmental delay 1. Beyond monogenic mitochondrial disease, MRPS28 expression is dysregulated in multiple cancer types. MRPS28 is upregulated in bladder cancer where CENPU promotes its expression to enhance tumor progression 2, and serves as part of a lactate metabolism-related prognostic signature in breast cancer 3. Conversely, MRPS28 expression is downregulated by benzyl isothiocyanate in glioblastoma 4 and responds to ionizing radiation in cervical carcinoma cells 5. MRPS28 is also implicated as a mitochondrial biomarker in follicular thyroid tumors 6 and major depressive disorder 7, suggesting broader roles in mitochondrial dysfunction-associated pathology.