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Despite its importance, the underlying molecular mechanisms of intrinsic plasticity remain poorly understood. In this study, a new ubiquitin ligase adaptor, protein tyrosine phosphatase receptor type N (PTPRN), is identified as a regulator of intrinsic neuronal excitability in the context of temporal lobe epilepsy. PTPRN recruits the NEDD4 Like E3 Ubiquitin Protein Ligase (NEDD4L) to Na<jats:sub>V<\/jats:sub>1.2 sodium channels, facilitating NEDD4L\u2010mediated ubiquitination, and endocytosis of Na<jats:sub>V<\/jats:sub>1.2. Knockout of PTPRN in hippocampal granule cells leads to augmented Na<jats:sub>V<\/jats:sub>1.2\u2010mediated sodium currents and higher intrinsic excitability, resulting in increased seizure susceptibility in transgenic mice. Conversely, adeno\u2010associated virus\u2010mediated delivery of PTPRN in the dentate gyrus region decreases intrinsic excitability and reduces seizure susceptibility. Moreover, the present findings indicate that PTPRN exerts a selective modulation effect on voltage\u2010gated sodium channels. 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