<p>Neurturin, a neurotrophic growth factor, has been identified as a potential treatment or reversal agent for neurodegenerative conditions. Although <i>Escherichia coli</i> is an appropriate host for recombinant protein expression, the production of proteins with disulfide bonds, such as neurturin, in this strain is frequently accompanied by the formation of inclusion bodies. In this study, the <i>Rosetta-gami</i> strain, which is well-suited for the accurate formation of disulfide bonds was employed for the soluble production of neurturin. Response surface methodology (RSM) was also used to investigate the effects of&#xa0;IPTG concentration, post-induction time and temperature on the soluble production of neurturin. The results showed that the highest yield of neurturin production occurred in the presence of 0.8&#xa0;mM of IPTG after 5.5&#xa0;h at 26 ºC. Fractional Factorial Design was used in the subsequent stage to screen the effects of culture medium components on the protein production. The best concentrations of yeast extract, tryptone and MgSO₄ to have a significant effect on total protein concentration were determined by RSM design to be 15&#xa0;g/l for both tryptone and yeast extract and 2.2&#xa0;g/l for MgSO₄. Finally, an experiment was carried out under optimized conditions to evaluate the yield of the process. The results demonstrated a notable enhancement in neurturin production following optimization, with an increase of 8.6-fold compared to the normal condition.</p> Graphical abstract <p></p>