MRPS2 (mitochondrial ribosomal protein S2) is a structural protein essential for assembling the mitoribosomal small subunit and facilitating mitochondrial translation 1. As a nucleus-encoded component of the dual-origin mitochondrial ribosome, MRPS2 is required for the translation of the 13 mtDNA-encoded polypeptides that comprise oxidative phosphorylation (OXPHOS) complexes 2. Defects in MRPS2 impair small subunit assembly, reducing steady-state MRPS2 protein levels and preventing proper mitoribosome formation, which subsequently inhibits mitochondrial translation and causes combined OXPHOS deficiency affecting multiple respiratory complexes 21. MRPS2 mutations cause combined oxidative phosphorylation deficiency-36 (COPD36), presenting with a variable clinical spectrum including severe metabolic decompensation, acute-onset hypoglycemia, lactic acidosis, sensorineural hearing loss, and developmental abnormalities 132. In patient-derived fibroblasts, MRPS2 variants show decreased transcript and protein expression, reduced Complex I and IV enzyme activities, impaired mitochondrial respiration, and altered mitochondrial morphology 1. Zebrafish modeling validated pathogenicity through developmental abnormalities and reduced Complex IV activity 1. The constellation of lactic acidemia, hypoglycemia, and sensorineural hearing loss should prompt investigation for MRPS2-related mitochondrial disease 2.