MAB21L1 is a putative nucleotidyltransferase required for embryonic development, particularly eye, cerebellar, craniofacial, and genital development 12. The protein contains a conserved nucleotidyltransferase fold structurally similar to cGAS 3, though in vitro nucleotidyltransferase activity has not been demonstrated 4. MAB21L1 binds single-stranded RNA 3 and associates with transcription factors regulating PAX6 (MEIS1, MEIS2, PBX1) and poly(A) RNA-binding proteins 4. During lens placode development, MAB21L1 modulates lens-specific gene expression (including Pitx3, Maf, and Sfrp2) and regulates DNA/nucleotide metabolic processes 5. Biallelic loss-of-function MAB21L1 mutations cause autosomal recessive cerebellar, ocular, craniofacial, and genital (COFG) syndrome with severe microphthalmia 5. Conversely, heterozygous missense variants at the Arg51 codon cause autosomal dominant microphthalmia and aniridia phenotypes via a gain-of-function mechanism 467. These Arg51 mutations reduce association with TBL1XR1 (NCoR complex component) and alter nuclear localization 47. MAB21L1 also regulates calvarial osteogenesis and bone resorption 8. Clinically, MAB21L1 variants account for approximately 1-3% of congenital microphthalmia cases and should be included in genetic testing panels for congenital eye disorders 7.