MAB21L1 is a putative nucleotidyltransferase structurally homologous to cyclic GMP-AMP synthase (cGAS) that plays a critical role in embryonic development, particularly eye morphogenesis. The protein binds single-stranded RNA and forms symmetric oligomers in vitro, though its catalytic nucleotidyltransferase activity in vivo remains unclear 1. During lens placode development, MAB21L1 functions as a nuclear factor modulating lens-specific gene expression and DNA/nucleotide metabolism, with loss of function triggering endoplasmic reticulum stress and downregulation of key developmental genes including Pitx3, Maf, and Sfrp2 2. MAB21L1 also associates with transcription factors regulating PAX6 and poly(A) RNA-binding proteins 3. Biallelic loss-of-function variants cause autosomal recessive cerebellar, ocular, craniofacial, and genital (COFG) syndrome, characterized by microphthalmia, corneal dystrophy, and extraocular abnormalities 2. Conversely, heterozygous missense variants—particularly at codon Arg51—cause autosomal dominant ocular syndromes including aniridia, microphthalmia, and blepharophimosis with anterior segment dysgenesis 345. These monoallelic variants likely exert gain-of-function effects that disrupt protein localization and associations with corepressor complexes 36. Currently, no disease-specific pharmacological therapies target MAB21L1, though understanding its role in transcriptional regulation and developmental signaling may inform future interventions for congenital eye defects.