Inositol polyphosphate phosphatase 4 A (INPP4A), a phosphoinositides phosphatase, is highly expressed in the central nervous system and plays a role in glutamate excitotoxicity and cell proliferation. Our aim was to investigate the expression of INPP4A in patients with temporal lobe epilepsy (TLE) and in a rat model of epilepsy. We assessed the expression of INPP4A in the temporal neocortex from 20 TLE patients. The result showed that INPP4A expression was significantly lower in TLE patients than in controls. To validate the results found in TLE patients, we assessed the expression of INPP4A in rat model. Rat epilepsy was induced by lithium-pilocarpine. Expression of INPP4A of rat models was assessed by immunohistochemistry, immunofluorescence, and Western blotting. INPP4A was expressed in the membrane and cytoplasm of neurons. In the hippocampus and neocortex of epileptic rats, INPP4A expression was first downregulated at the 24 h after seizures and maintained decreased levels at 72 h, 7 days, 14 days, 30 days, and 60 days, respectively. These results suggest that a decreased expression of INPP4A in the brain may be associated with TLE.