AUTS2 is a transcriptional regulator with dual nuclear and cytoplasmic functions essential for neurodevelopment 1. In the nucleus, AUTS2 functions as a component of a PRC1-like Polycomb complex that mediates transcriptional activation through altered histone H2A ubiquitination 2. This complex regulates genes critical for cortical development, including control of neural progenitor cell proliferation and G1/S transition gene expression 3. In the cytoplasm, AUTS2 promotes neuronal migration, axon/dendrite elongation, and actin cytoskeleton reorganization through activation of RAC1 signaling 1. AUTS2 mutations cause AUTS2-related syndrome, characterized by intellectual disability, autism spectrum disorder, developmental delay, and microcephaly 4. The severity of neurological symptoms correlates with mutation location—variants affecting both long and short AUTS2 isoforms present with recognizable facial features and microcephaly, while variants affecting only the longer isoform show predominantly behavioral disorders 4. Cerebral organoid models demonstrate that pathogenic variants impair neural progenitor proliferation and disrupt cortical growth 3. AUTS2 is expressed in specific neuronal populations including pyramidal neurons and Purkinje cells, localizing primarily to cell nuclei where it regulates transcription and RNA metabolism 5.