UBQLN4 regulates seizures by promoting the proteasomal degradation of GluN2B

Ubiquilin 4 (UBQLN4) is an important molecule that regulates protein degradation through the ubiquitin-proteasome pathway. This study found that UBQLN4 expression is significantly reduced in a chronic epilepsy mouse model induced by kainic acid, primarily localized in neurons and widely distributed at excitatory post-synapses. Experiments involving adeno-associated virus-mediated overexpression or knockdown of UBQLN4 indicate that a reduction in UBQLN4 increases susceptibility to and severity of epilepsy, while its overexpression has a protective effect. Mechanistic studies show that UBQLN4 regulates the degradation of the N-Methyl d-Aspartate 2B Subunit (GluN2B) via the proteasome pathway, thereby affecting synaptic function. This research reveals the critical role of UBQLN4 in epilepsy and provides a potential new target for the treatment of epilepsy.