METTL5 is a catalytic methyltransferase that forms a heterodimeric complex with TRMT112 to install N6-methyladenosine (m6A) modifications at position 1832 of 18S ribosomal RNA 1. This m6A modification resides in the decoding center of 18S rRNA and is essential for proper translation initiation and function 2. Beyond its canonical rRNA methylation role, METTL5 has emerged as a critical regulator of selective protein translation in multiple cancer contexts. In hepatocellular carcinoma, METTL5 enhances USP5 translation, stabilizing c-Myc and promoting glycolytic reprogramming 3. In ovarian cancer, METTL5 modulates ATF4 translation to suppress ferroptosis and enable immune evasion 4. Similarly, METTL5 in liver cancer regulates CXCL16 translation to exclude CD8+ T cells from the tumor microenvironment 5. In multiple myeloma, METTL5 influences SEPHS2-mediated selenoprotein synthesis, promoting cell survival 6. METTL5 dysregulation is associated with intellectual developmental disorder, autosomal recessive 72, and elevated METTL5 expression correlates with poor prognosis across multiple malignancies 7. These findings establish METTL5 as a pleiotropic regulator of translation with significant implications for both developmental biology and cancer therapeutics.