Proteins are essential for the construction of living organisms

regulation of physiological functions

and energy supply for life activities. With the introduction of proteomics technology and the rapid development of biotechnology

the demand for efficient protein separation is increasing. The development of effective protein separation techniques is essential to advance proteomics research and biotechnology applications. This review aims to summarize recent advances in the field of protein separation using polymeric materials

focusing on the design

function and application potential of these materials. The review begins with a classification of polymers according to their interaction mechanism with proteins

which includes size sieving

hydrophobic interactions and electrostatic interactions. These interactions can be used for selective protein capture and purification. Neutral polymers are firstly introduced and classified into hydrophilic and hydrophobic polymers

which separate proteins via size sieving and hydrophobic interactions

and are known for their abilities in constructing stable three-dimensional network structures

reducing non-specific adsorption and maintaining protein activity. The second focus is placed on the separation of positively and negatively charged proteins by electrostatic attraction or repulsion

and the introduction of abundant charged functional groups on polymeric materials can provide active sites for protein binding. Tunable charge systems are also discussed

with a focus on composites that can be switched between cationic

neutral and anionic states. Weak polyelectrolytes that undergo reversible protonation and deprotonation are commonly used in the tunable system as their charge state changes in response to changes in pH or other environmental factors. This property facilitates the control of protein adsorption and desorption processes. The application of stimuli-responsive polymers with changeable physical or chemical properties in response to external stimuli such as temperature

pH

light

or electric fields

in improving protein capture efficiency and selectivity is also reviewed. Finally

this review predicts future trends in protein separation technology

envisioning more efficient

precise

and intelligent systems capable of achieving higher purity and yield of protein separation. The development of cost-effective

scalable methods to meet the stringent requirements of personalized therapies and industrial biopharmaceutical production remains a challenge. The combination of information technology and traditional experimental science will pave the way for next-generation protein separation tools that address these challenges

making a significant contribution to the advancement of life sciences and healthcare.