There are some technical challenges when performing open modification searching that are exacerbated by the large search space in immunopeptidomics. Efficient new tools tackle these technical challenges and have been starting to integrate rescoring . However, it is important to note that currently most PTMs found with open modification searching might not be supported by the underlying predictors. In this case, transfer learning can be used , as well as emerging algorithmic solutions that can predict peptide properties for unseen PTMs . Additionally, even though several approaches have been proposed to control the FDR in open modification searching , further research is necessary to investigate how the FDR behaves and to ensure that PSM rescoring does not introduce biases.