METTL22 is a protein-lysine N-methyltransferase that catalyzes trimethylation of KIN17 at lysine 135, a residue within KIN17's winged helix domain 1. This methylation regulates KIN17's chr16 association; METTL22 overexpression displaces KIN17 from chr16 to the cytoplasm, suggesting methylation controls KIN17's DNA/RNA-binding functions in replication, repair, and pre-mRNA processing 1. METTL22 is essential for hematopoietic stem/progenitor cell (HSPC) specification during differentiation from pluripotent stem cells, with confirmed importance for both zebrafish HSPC development and human HSC maintenance 2. In disease context, METTL22 autoantibodies are detected at elevated frequency in narcolepsy patients from both vaccine-associated and sporadic cases, implicating potential autoimmune mechanisms in this sleep disorder 3. Additionally, METTL22 is a predicted target of miR-218-5p in chr16 stress-induced depression pathways, where it may participate in stress-responsive chr16 modifications affecting central nervous system gene expression 4. These findings establish METTL22's role in epigenetic regulation of critical cellular processes spanning development, neural function, and immune response.