MRPL43 (mitochondrial ribosomal protein L43) is a structural component of the mitochondrial large ribosomal subunit that functions in mitochondrial translation [GO Annotations]. The gene is regulated by a conserved bidirectional promoter shared with TWINKLE, a mitochondrial DNA helicase 1. MRPL43 expression is subject to complex cis-acting regulation: a 97 kb eQTL spanning the gene exhibits antagonistic effects across expression stages, with one allele increasing mRNA and ribosome occupancy but decreasing protein abundance through coordinated effects of three linked variants affecting transcription, splicing, and microRNA binding 2. Clinically, MRPL43 variants are associated with neurodegenerative diseases. A heterozygous variant (c.241A>C:p.N81H) is associated with dementia with Lewy bodies (DLB) in Japanese populations 3, and splicing introns in MRPL43 are linked to Alzheimer's disease (AD) susceptibility in European ancestry populations 4. Additionally, the miR-608 rs4919510 polymorphism may regulate MRPL43 expression and influence cancer susceptibility, with knockdown of MRPL43 inhibiting colorectal cancer cell proliferation and promoting apoptosis 5. MRPL43 expression is upregulated in response to antidiabetic therapy, particularly sitagliptin 6, suggesting involvement in metabolic stress responses.