SPOUT1 is an S-adenosyl-L-methionine-dependent RNA methyltransferase that catalyzes N3 methylation of uridine in 28S rRNA 1. Beyond its catalytic function, SPOUT1 serves a critical structural role in mitosis by maintaining centrosome attachment to spindle poles during metaphase and promoting chromosome 9 23. The protein likely facilitates centrosome maturation by recruiting AKAP9 to centrosomes in early mitosis 3. Additionally, SPOUT1 regulates miRNA-145 expression through direct hairpin binding and post-transcriptional mechanisms 4. Bi-allelic SPOUT1 variants cause SpADMiSS (SPOUT1 Associated Development delay Microcephaly Seizures Short stature), an autosomal recessive neurodevelopmental disorder 56. Disease-associated missense variants cluster in the catalytic domain, exhibiting reduced methyltransferase activity and compromised centrosome tethering 5. In zebrafish models, spout1 mutations produce microcephaly with increased apoptosis, likely reflecting defective cell cycle progression 5. The dual functionality of SPOUT1—combining RNA modification with mitotic spindle organization—explains how catalytic mutations cause both molecular and cellular phenotypes underlying neurodevelopmental disease.