Sturge-Weber syndrome (SWS), a rare neurovascular disorder associated with a GNAQ gene mutation, presents distinct clinical features, including a facial port-wine birthmark, glaucoma, and various neurological symptoms. Despite these characteristics, the molecular complexity of neurovascular cross-talk remains poorly understood. This study aims to unravel Gαq regulation in neural cells, focusing on surface marker expression. To study surface marker regulation, CRISPR-mediated Gαq knockouts were generated in Lund human mesencephalic cells (LUHMES; neural) and pluripotent stem cells (embryonic). The pluripotent stem cell line was further neurally differentiated to a neural stem cell-like stage using a dual SMAD inhibition protocol. Surface marker screening in Gαq knockout LUHMES cells exhibited increased CD119 (Interferon gamma receptor 1) and CD138 (Syndecan 1) expression and decreased CD82 (KAI1, tetraspanin-27) levels. Further validation in neurally differentiated Gαq knockout pluripotent stem cells revealed reduced CD82 expression, aligning with the results from LUHMES cells. Overexpressing Gαq in HEK293T cells led to decreased CD119 and CD138 expression, with no change in CD82 levels. The specificity of Gαq-mediated modulation for CD82 in neural proliferative cells suggests a unique regulatory role, implicating this tetraspanin involvement in the neurovascular interplay of Sturge-Weber syndrome, while CD119 and CD138 modulation appears conserved across cell types tested here. These findings contribute to a better understanding of the intricate relationship between Gαq and surface proteins, shedding light on the molecular dynamics in SWS pathology.