MRPL46 is a mitochondrial ribosomal protein component of the large subunit (60S) involved in mitochondrial translation 1. The protein is encoded by the C15orf4 gene, which shows evolutionary conservation across species and is positioned on chromosome 15 1. MRPL46 functions as a structural constituent of the mitochondrial ribosome, contributing to the translational machinery in the mitochondrial matrix. Disease relevance has emerged through multi-omics studies linking MRPL46 to major depressive disorder (MDD). Elevated methylation of MRPL46 (cg00200755) is associated with increased MDD risk, suggesting epigenetic regulation of mitochondrial translation capacity may influence neuropsychiatric phenotypes 2. Additionally, MRPL46 has been identified as a candidate biomarker in schizophrenia-associated cognitive impairment, with expression levels negatively correlated with natural killer cell infiltration in affected individuals 3. These associations suggest mitochondrial dysfunction through altered expression of ribosomal proteins may contribute to neuropsychiatric disease pathophysiology. Clinically, MRPL46 represents a potential therapeutic target for addressing mitochondrial dysfunction in mood and cognitive disorders, though mechanistic validation in larger cohorts remains necessary.