Fig. 5.

Model summarizing channel-dependent and channel-independent roles of α₂δ proteins. Mutations of α₂δ genes can affect expression levels, protein structure, and splicing. These alterations have consequences on calcium channel–dependent functions (membrane expression, current modulation, channel subtype–specific functions), and channel-independent functions (extracellular and/or trans-synaptic interactions and signaling pathways). The two mechanisms should not be considered entirely independent as they are likely influencing each other. For example, alterations in synapse differentiation will also affect VGCC expression with further consequences on neuronal excitability and synaptic transmission