Objective To explore the neuroprotective effects and autophagy regulation of 4-aminopyridine （4-AP） as a transmembrane protein 175 （TMEM175） inhibitor in Parkinson disease （PD） mice. Methods A 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP）-induced PD mouse model was used， involving 60 C57BL/6 mice， which were randomly divided into four groups， including control group， MPTP group， 4-AP group and 4-AP+MPTP group， with 15 mice in each group. The effects of 4-AP on dopamine neurons， TMEM175 expression and autophagy levels were assessed by behavioral testing， molecular docking， immunohistochemistry， Western blot， RT-qPCR and ELISA. Results Behavioral analysis showed that the speed of mice in MPTP group was （5.4±1.1） cm/s， which was lower than that of （6.8±0.6） cm/s in control group and （6.4±0.9） cm/s in 4-AP+MPTP group， and the difference was statistically significant （all P＜ 0.05）. The free movement time and forelimb grip strength of mice in MPTP group were （155.1±9.0） s and （173.8±13.5） g，respectively， which were lower than those of 4-AP+MPTP group （164.2±9.2） s and （191.3±16.1） g， respectively， and the differences were statistically significant （all P ＜ 0.05）. Compared with MPTP group， the expression of TMEM175 protein （P ＜ 0.001） and mRNA （P ＜ 0.01） was decreased， and the levels of TH protein （P ＜ 0.05） and mRNA （P ＜ 0.01） were elevated in 4-AP+MPTP group of mice， and the differences were statistically significant. The levels of autophagy markers LC3A （P＜ 0.01） and Beclin-1 （P＜ 0.001） were increased in MPTP group， whereas the expression was reduced in 4-AP+MPTP group （P ＜ 0.05）， and the differences were statistically significant. Conclusions 4-AP improves motor function and reduces dopamine neuron loss in PD mice by targeting TMEM175 channels and regulating autophagy-related protein levels.