METTL18 is a histidine-specific methyltransferase that catalyzes N3-tau-methylation of histone H245 on the ribosomal protein RPL3 1. This modification regulates translation elongation by specifically slowing ribosome traversal on tyrosine codons, allowing adequate time for proper nascent protein folding and preventing cellular aggregation of tyrosine-rich proteins 2. METTL18 localizes to the nucleolus and nucleus and is essential for optimal ribosome biogenesis, as METTL18 knockout cells display altered pre-rRNA processing and decreased polysome formation 1. Beyond its canonical ribosomal function, METTL18 plays critical roles in disease pathogenesis. In pancreatic tissue, METTL18 maintains proteostasis; knockout mice show diabetic phenotypes, pancreatitis-associated protein aggregation, and compromised protein folding 3. In HER2-negative breast cancer, elevated METTL18 expression associates with poor prognosis and promotes metastatic responses through an METTL18-RPL3-HSP90-actin-Src regulatory axis 4. Additionally, METTL18 expression is dysregulated in fibromyalgia syndrome, suggesting broader pathophysiological relevance 5. These findings establish METTL18-mediated histidine methylation as a physiologically important modification regulating proteostasis and identify METTL18 as a potential therapeutic target in cancer and metabolic diseases.