As the fastest growing sectors of the pharmaceutical industry, most therapeutic proteins have complex post-translational modifications for efficient secretion and drug efficacy and stability maintenance. PTMs can affect the activity, stability, and function of a protein. Misfolding, aggregation, variable glycosylation, oxidation of methionine, deamination of asparagine and glutamine, and proteolysis are common types of protein modifications. Incorrect modifications of protein therapeutic may result in immune response, or even serious side effects. These modifications pose a great challenge for accurate and consistent bioprocessing and a comprehensive analysis of protein modifications is a necessary.