Objective To explore the effect of the Trim44 gene in the nervous system, Trim44 conditional knockout rats were used to analyze behavioral abnormalities and pathological changes in the brain. Methods TRIM44 expression in brain tissue was detected by Western blot and immunohistochemistry. Neuronal apoptosis was determined by TUNEL staining. Behavioral changes of knockout rats were assessed by Morris Y, Morris water, and food maze tests. Abnormal expression of apoptosis-related proteins was detected by Western blot. Results TRIM44 was highly expressed in brain tissues of adult rats. The knockout efficiency of Trim44 in brain tissues was 67%. Trim44 knockout decreased learning and memory abilities, increased neuronal apoptosis, and expression of active caspase 3 and 9 proteins in aged rats. Conclusions Trim44 knockout promotes neuronal apoptosis and impairs learning and memory abilities in rats. These result suggest that TRIM44 plays an important role in the nervous system, and the Trim44 knockout rat model can be used for further mechanism exploration.