Dystroglycan 1

Dystroglycan 1 (DAG1) is a transmembrane glycoprotein that acts as a cell adhesion receptor and extracellular matrix scaffold, linking the dystrophin-associated protein complex to the cytoskeleton (UniProt: Q14118). The protein binds laminin and agrin to regulate extracellular matrix assembly, synaptic formation, and signaling cascades involving PI3K/AKT and MAPK pathways, with roles in photoreceptor and inhibitory synapse maintenance. It is also a receptor for certain arenaviruses and Mycobacterium leprae (UniProt: Q14118).

DAG1 is primarily associated with muscular dystrophy-dystroglycanopathies, a group of autosomal recessive disorders ranging from limb-girdle muscular dystrophy with intellectual disability to congenital forms with severe brain and eye anomalies including cobblestone lissencephaly (UniProt: Q14118, MIM 613818, 616538).

In Alzheimer's Disease, DAG1 is significantly upregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of 0.38 across subcellular fractions (Chaparral AD proteomics). This elevation may reflect compensatory responses in synaptic stability or extracellular matrix remodeling occurring in AD pathology.