Intrinsic plasticity, a fundamental process enabling neurons to modify their intrinsic properties, plays a crucial role in shaping neuronal input-output function and is implicated in various neurological and psychiatric disorders. Despite its importance, the underlying molecular mechanisms of intrinsic plasticity remain poorly understood. Here, we identified a new ubiquitin ligase adaptor, protein tyrosine phosphatase receptor type N (PTPRN), as a regulator of intrinsic neuronal excitability in the context of temporal lobe epilepsy. We discovered that PTPRN facilitates NaV1.2 sodium channel endocytosis. Knockout of PTPRN in hippocampal granule cells led to augmented NaV1.2-mediated sodium currents and higher intrinsic excitability, resulting in increased seizure susceptibility in transgenic mice. Conversely, adeno-associated virus-mediated delivery of PTPRN in the dentate gyrus region decreased intrinsic excitability and reduced seizure susceptibility. Further, we identified a 133-amino acid fragment of PTPRN capable of reversing the aberrant function of mutated NaV1.2, indicating the therapeutic potential of this fragment in NaV1.2-related epilepsy. Our results demonstrate that PTPRN plays a significant role in regulating intrinsic excitability and seizure susceptibility and may serve as a potential alternative for the treatment of epilepsy.