Phf24 interacts with G_αi subunit and facilitates GABA_B receptor functions. We previously demonstrated that Phf24 expression was markedly down-regulated in Noda epileptic rat (NER) (Behav. Genet., 47, 609, 2017). To clarify the role of Phf24 in regulating seizure susceptibility, we created the novel animal model, Phf24-knockout (KO) rats, and analyzed their behavioral phenotypes. Seizure susceptibility of Phf24-KO rats was assessed using chemically- and electrically-induced seizure tests. Behavioral score and incidence of seizures induced by pentylenetetrazole (PTZ, 30-40 mg/kg) and pilocarpine (300 mg/kg) were significantly increased in Phf24-KO rats than in control (F344) rats. Phf24-KO rats also showed higher sensitivity to electrical shock-induced seizures. In addition, PTZ-induced kindling (30 mg/kg/day, 10 days) was significantly facilitated by the Phf24-KO. Furthermore, immunohistochemical analysis of c-Fos expression, a biological marker of neural excitation, revealed that Phf24-KO rats showed a significantly higher Fos expression than control animals in the cerebral cortex, amygdala, hippocampus and thalamus. These results suggest that Phf24 play a crucial role in controlling the susceptibility to epileptic seizures, which is probably involved in epileptogenicity of NER.