Proteins can be secreted from a host organism with the aid of N-terminal secretion signals. The budding yeast Pichia pastoris (Komagataella sp.) is widely employed to secrete proteins of academic and industrial interest. For this yeast， the most commonly used secretion signal is the N-terminal portion of pre-pro-α-factor from Saccharomyces cerevisiae. However， this secretion signal promotes posttranslational translocation into the endoplasmic reticulum (ER)， so proteins that can fold in the cytosol may be inefficiently translocated and thus poorly secreted. In addition， if a protein self-associates， the α-factor pro region can potentially cause aggregation， thereby hampering export from the ER. This study addresses both limitations of the pre-pro-α-factor secretion signal.