DOP1B (DOP1 leucine zipper like protein B) is a membrane trafficking regulator located on chromosome 21 within the Down syndrome critical region. Its primary function involves regulating endosomal sorting and cargo protein trafficking, working with ATP9A and MON2 to direct SNX3 retromer-mediated recycling of Wntless away from lysosomal degradation 1. This function is essential for maintaining proper Wnt secretion and morphogenic gradient formation. DOP1B exhibits developmentally regulated expression in key brain structures including the cerebellum, hippocampus, and cortex 2, tissues notably altered in Down syndrome. The gene is also expressed across ocular tissues including the lens, iris, cornea, and retina 3. Dysregulation of DOP1B has been associated with developmental pathology: homozygous mutations cause Peters anomaly, a corneal developmental disorder 3, while heterozygous variants have been identified in keratoconus families 4. As a chromosome 21 gene, DOP1B overexpression may contribute to neurological alterations and cognitive dysfunction in Down syndrome 5. Recent proteomic evidence suggests DOP1B promotes osteogenic differentiation of dental pulp stem cells 6. These findings indicate DOP1B plays multifaceted roles in developmental patterning and tissue-specific differentiation beyond previously recognized brain functions.