MRM2 is a mitochondrial S-adenosyl-L-methionine-dependent methyltransferase that catalyzes the formation of 2'-O-methyluridine at position 1369 (Um1369) in the 16S mitochondrial large ribosomal subunit (mtLSU) rRNA 123. This modification occurs within the peptidyl transferase center, a universally conserved domain essential for protein synthesis 12. The methylation activity may require prior modification at position 1370 by MRM3, indicating interdependent modifications 3. Beyond its methyltransferase function, MRM2 serves a critical structural role in late-stage mtLSU assembly that is independent of its enzymatic activity 3. Loss of MRM2 results in disordered RNA domains, partial occupancy of ribosomal proteins, and accumulation of assembly factors, leading to defective mitoribosome maturation 3. MRM2 depletion causes respiratory incompetence due to impaired mitochondrial protein translation 1. Pathogenic variants in MRM2 are associated with mitochondrial DNA depletion syndrome 17 and dystonic movement disorders 4. The protein functions as a quality control checkpoint during mtLSU assembly, ensuring proper mitoribosome formation essential for mitochondrial respiratory function 35.