MRPL40 encodes mitochondrial ribosomal protein L40, a component of the large ribosomal subunit essential for mitochondrial protein synthesis and proteostasis 1. The protein functions within mitochondrial ribosomes to translate mitochondrial DNA-encoded genes, with haploinsufficiency leading to reduced mitochondrial protein levels and ATP production 2. MRPL40 is located within the 22q11.2 chr22 region, and its hemizygous deletion contributes to 22q11.2 deletion syndrome pathogenesis through multiple mechanisms 3. Mechanistically, MRPL40 haploinsufficiency disrupts mitochondrial calcium homeostasis by impairing calcium extrusion through the mitochondrial permeability transition pore, leading to abnormally high cytosolic calcium transients in presynaptic terminals 3. This results in deficient short-term synaptic plasticity and working memory impairments characteristic of schizophrenia 3. During neurodevelopment, MRPL40 regulates neural stem and progenitor cell proliferation, with mutations causing microcephaly and behavioral deficits 4. The gene also shows clinical significance in cancer, where altered expression correlates with poor prognosis in breast cancer patients and promotes colorectal cancer cell proliferation and migration 56. Additionally, MRPL40 has been identified as a potential biomarker for primary open-angle glaucoma 7.