Protocadherin-8 (PCDH8)

Protocadherin-8 (PCDH8) is an integral membrane protein belonging to the non-clustered delta-2 subgroup of the protocadherin family within the cadherin superfamily[1][2][5]. It is primarily expressed in the central nervous system, where it mediates calcium-dependent cell adhesion and plays a key role in neural development, synaptic organization, and the maintenance of specific neuronal connections[1][2][5][8]. Functionally, PCDH8 is implicated in activity-induced synaptic reorganization and the regulation of dendritic spine density, possibly through modulating the internalization of classical cadherins.[5] Beyond neural contexts, PCDH8 acts as a tumor suppressor in several cancers, where its downregulation is associated with increased proliferation, migration, invasion, and epithelial–mesenchymal transition of tumor cells; these actions are at least partly mediated by suppression of the AKT/VEGF signaling pathways[3][4][7]. Mutations or epigenetic silencing of PCDH8 are linked to certain developmental and epileptic encephalopathies and may play roles in other neurodevelopmental disorders[5]. No direct-acting drugs against PCDH8 are in clinical use, and no specific drug safety challenges have been documented for this target.

Other names

Protocadherin-8PCDH8PAPCARCADLINArcadlinparaxial protocadherin

null (no approved drugs specifically modulate PCDH8; functionally, it exerts tumor-suppressive effects through inhibition of AKT signaling and suppression of epithelial–mesenchymal transition)