Malloy_2022_Int.J.Mol.Sci_23_9184

The concerted action of voltage-gated ion channels in the brain is fundamental in controlling neuronal physiology and circuit function. Ion channels often associate in multi-protein complexes together with auxiliary subunits, which can strongly influence channel expression and function and, therefore, neuronal computation. One such auxiliary subunit that displays prominent expression in multiple brain regions is the Dipeptidyl aminopeptidase-like protein 6 (DPP6). This protein associates with A-type K(+) channels to control their cellular distribution and gating properties. Intriguingly, DPP6 has been found to be multifunctional with an additional, independent role in synapse formation and maintenance. Here, we feature the role of DPP6 in regulating neuronal function in the context of its modulation of A-type K(+) channels as well as its independent involvement in synaptic development. The prevalence of DPP6 in these processes underscores its importance in brain function, and recent work has identified that its dysfunction is associated with host of neurological disorders. We provide a brief overview of these and discuss research directions currently underway to advance our understanding of the contribution of DPP6 to their etiology.