METTL17 (methyltransferase-like 17) is a mitochondrial ribosome assembly factor that binds at the interface of the head and body domains of the mitochondrial small ribosomal subunit (mt-SSU), preventing head domain compaction and occluding the mRNA channel 1. Though structurally retaining methyltransferase characteristics and S-adenosyl-L-methionine binding capacity, METTL17 is functionally inactive as a methyltransferase 2. METTL17 harbors a [Fe4S4]2+ cluster essential for its stability and acts as an Fe-S cluster checkpoint, promoting mitochondrial translation of oxidative phosphorylation proteins only when Fe-S cofactors are replete 3. During mitoribosome biogenesis, METTL17 functions in early assembly stages and acts as a platform for recruiting Mettl15, facilitating the transition to late assembly 4. Beyond mitoribosomal roles, METTL17 regulates mitochondrial RNA methylation (m4C, m5C, m3C, m7G, m6A), modulating mitochondrial protein synthesis and cellular energy metabolism 5. METTL17 upregulation correlates with ferroptosis resistance and tumorigenesis in colorectal cancer, while also promoting oral cancer and hepatocellular carcinoma development 567. In ankylosing spondylitis, METTL17 suppresses inflammation by mediating STAT1 RNA methylation 8. Mutations in Fe-S cluster delivery factors affecting METTL17 cause mitochondrial dysfunction and multiple mitochondrial dysfunction syndrome 9.