MRPS21 is a mitochondrial ribosomal protein that functions as a structural component of the mitochondrial small ribosomal subunit, participating in mitochondrial translation through RNA binding 1. As a nuclear-encoded mitochondrial gene, MRPS21 contributes to mitochondrial protein synthesis, which is essential for oxidative phosphorylation and cellular energy metabolism 2. In disease contexts, MRPS21 expression has significant clinical relevance. The gene was identified as one of 14 mitochondrial ribosomal proteins significantly upregulated in hepatocellular carcinoma (HCC) tissue compared to normal samples, demonstrating good diagnostic performance by receiver-operating characteristic curve analysis 1. Additionally, MRPS21 was identified in a genomic region (1q21.3) with suggestive evidence of association with progression from islet autoimmunity to type 1 diabetes, indicating a potential role in autoimmune disease pathogenesis 3. In skeletal muscle, MRPS21 expression increased following exercise training, correlating with enhanced mitochondrial function and oxidative capacity 2. These findings suggest MRPS21 serves as a biomarker for both cancer diagnosis and disease progression monitoring, while its regulation reflects cellular metabolic demands across different physiological contexts.