MAB21L2 is a developmentally critical gene required for multiple aspects of embryonic eye development and skeletal morphogenesis. Primary function: MAB21L2 regulates retinal progenitor cell (RPC) proliferation and differentiation during retinogenesis 1, controlling temporal transitions between cell proliferation and differentiation. Mechanism: MAB21L2 interacts with heat shock proteins HSPA5 and HSPA8 2, and its expression is regulated by conserved non-coding regulatory elements that bind the transcription factor Otx2 3. The protein is essential for optic cup morphogenesis, lens development, cornea differentiation, and choroid fissure closure 4. Disease relevance: Pathogenic variants in MAB21L2 cause microphthalmia/coloboma and skeletal dysplasia syndrome 56. Both missense mutations (e.g., p.Arg51Gly) and upstream deletions affecting regulatory elements result in ocular defects 37. Mouse models with MAB21L2 mutations display anophthalmia, skeletal abnormalities including joint fusion, and shortened limbs 6. Clinical significance: MAB21L2 variants account for a subset of anophthalmia, microphthalmia, and coloboma cases, contributing approximately 20% of childhood visual impairment when considered across genetic eye disorders 3. Genetic testing and prenatal diagnosis are available for affected families 7.