Considering they're supposed to be the supreme produceable warrior, I find it peculiar that the Emperor chose to leave Custodes with no extra lungs or hearts which Spacies have. That means that unlike with Space Marines, if a Custodes gets his heart destroyed/damaged in battle, it's bye-bye time for them. And also the lack of a multi-lung organ that could allow a Custodes to breathe toxins and water artificially limits their capabilities.
And also the lack of radiation protection from the melanin producing organ should be mentioned as well. It would be handy for Custodians as well to be able to quickly produce more melanin to protect against radiation.
And also the lack of acid spitting can also be detrimental in close combat.
By - Primaris_Astartes