ARHGAP11B is a human-specific protein that plays a critical role in neocortex expansion through basal progenitor amplification 1. Unlike its parental gene ARHGAP11A, ARHGAP11B lacks GTPase activator activity, which is required for its function in promoting progenitor proliferation 1. Mechanistically, ARHGAP11B localizes to mitochondria where it interacts with the adenine nucleotide translocase (ANT) to inhibit the mitochondrial permeability transition pore (mPTP), increasing mitochondrial Ca²⁺ concentration and stimulating glutaminolysis—the conversion of glutamine through glutamate to α-ketoglutarate in the TCA cycle 2. This metabolic rewiring supports basal progenitor proliferation 2. ARHGAP11B is necessary and sufficient to establish elevated basal progenitor levels characteristic of fetal human neocortex 3. In transgenic mice expressing human ARHGAP11B, neocortical expansion persists into adulthood with increased upper-layer neurons, correlating with enhanced memory flexibility and reduced anxiety 4. Evidence from marmoset studies confirms ARHGAP11B drives neocortex expansion and folding in primates 5. Clinically, ARHGAP11B deletions have been identified in autism spectrum disorder patients 6, suggesting its relevance to neurodevelopmental pathology. The gene likely contributed substantially to human cognitive evolution through its role in expanding neural progenitor populations.