Glycogen, the largest macromolecule of the cytosol, plays a unique and fundamental role in the brain. It is the reservoir and buffer for the molecules that sustain the brain’s energy (glucose), proteins (glucosamine for protein glycosylation), and neurotransmitters (glutamate and GABA carbon backbones). For glycogen to serve these functions, it needs to always be soluble. Results emanating from gene discoveries in rare pediatric and adult neurological diseases have uncovered a cadre of enzymes, most E3 ubiquitin ligases, that coordinate the construction and reconstruction of perfectly spherical soluble glycogen particles. Our lab is dedicated to obtaining a comprehensive understanding of this molecular engineering of glycogen, upon which all brain function depends. In addition, the lab is engaged in a series of gene replacement therapy projects in various epileptic and neurodegenerative diseases of children, including but not limited to the genes of the above enzymes of glycogen architecture. These gene therapy projects extend from the bench into clinical trial.