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Therapeutic glycoproteins, which are produced in different expression systems are effective as biopharmaceuticals in medical applications and glycan engineering technology can open a new world to facilitate production of these proteins to overcome some pharmacological problems by humanizing the biopharmaceuticals. Also, the recognition of the role of glycosylation upon proteomics inconstancies of therapeutic proteins under manufacturing is critical for safety and non-immunogenic production. In this review, we tried to describe some important therapeutic glycoproteins and focused on some proteomics challenges of these proteins, which are improved by glycosylation.