SP9 is a transcription factor of the Krüppel-like factor/specificity protein family that plays a central role in neurodevelopment, particularly in interneuron development and migration 1. SP9 functions as a sequence-specific DNA-binding transcription factor that coordinately regulates gene expression with its homolog Sp8 in the developing nervous system 2. In the postnatal telencephalon, Sp8 and Sp9 coordinately regulate olfactory bulb interneuron development, with double mutants showing reduced interneuron numbers due to defects in neuronal differentiation, tangential and radial migration, and increased cell death, accompanied by failure to express Prokr2 and Tshz1 genes 2. Beyond neural development, SP9 regulates IL-10RB gene expression in the brain, where IL-10RB elevation has been detected in Alzheimer's disease patients and animal models 3. Clinically, de novo heterozygous SP9 variants cause a novel interneuronopathy characterized by intellectual disability, autism spectrum disorder, and epilepsy with variable expressivity 1. Missense variants affecting glutamate 378 produce severe epileptic encephalopathy through hypomorphic and neomorphic DNA-binding effects, whereas loss-of-function variants result in milder phenotypes with epilepsy, developmental delay, and autism spectrum disorder 1.