PRRT2 as an auxiliary regulator of Nav channel slow inactivation.

PRRT2 enhances Nav channel slow inactivation and delays recovery, affecting neuronal excitability from zebrafish to humans.

• Why it matters: Understanding endogenous regulators of Nav channel slow inactivation is crucial because disruptions are linked to neurological and cardiac disorders, yet their mechanisms remain unclear.
• What they did: The study used molecular and physiological approaches to identify PRRT2 as a native regulator, demonstrating its role in promoting slow inactivation and forming complexes with Nav channels in vitro and in vivo.
• The result: PRRT2 deficiency impairs Nav channel slow inactivation in mouse cortical neurons, reducing resilience to hyperexcitability, which suggests PRRT2's importance in maintaining cortical stability and preventing disease.