The goal of this Program Announcement is to solicit applications on lysosomal storage disorders (LSDs) focused on improving CNS treatment outcomes, enhancing the effectiveness of delivery and targeting of cells, enzymes, drugs and genes into the brain, and developing novel therapeutic modalities, such as implantable biocapsules and micro-electro-mechanical systems (MEMS)-based devices. Lysosomal storage disorders constitute a group of recessive genetic diseases resulting from cellular enzymatic deficiencies of acid hydrolases that normally catalyze the metabolism of glycoproteins, glycolipids and other macromolecules, or from defects in transporter proteins leading to pathogenic accumulation of these substances in lysosomes. Treatment modalities for LSDs are currently limited to bone marrow transplantation (BMT) and enzyme replacement therapy (ERT). These approaches while providing significant promise for treatment of the visceral manifestations of LSDs, do little to address CNS pathologies for this group of disorders. Thus this announcement specifically encourages the transition from basic studies in LSDs to translational research for improved delivery of therapeutic cells, proteins, genes, and small molecules across the blood-brain barrier.