Cortical astrocytes expressing lipoprotein receptor-related protein 4 (LRP4) represent a specialized GFAP-negative subpopulation that clusters along the brain's surface layer and forms direct physical contacts with arterial vessels. When researchers depleted these cells in mouse models, cerebral blood vessel diameter decreased alongside reduced branching density, while laminin-α5 levels—a critical basement membrane protein—dropped significantly. The vascular dysfunction coincided with compensatory increases in traditional GFAP-positive astrocytes and activated microglia. This discovery reveals a previously unrecognized division of labor within brain support cells, where LRP4+ astrocytes function as specialized vascular maintenance units distinct from conventional astrocytes. The finding carries particular relevance for neurodegenerative disease research, as these protective cells diminish in Alzheimer's models while avoiding amyloid plaque sites that attract conventional astrocytes. Unlike traditional astrocytes that respond to pathological proteins, LRP4+ cells appear to prioritize vascular integrity through extracellular matrix regulation. This represents a paradigm shift from viewing astrocytes as a uniform population toward recognizing functionally distinct subtypes with specialized roles in brain health, potentially opening new therapeutic avenues for vascular-related cognitive decline.