###### Abstract  
Proteins are one of the primary building blocks that have significant functional properties to be applied in food and pharmaceutical industries. Proteins could be beneficial in their concentrated products or isolates, of which membrane-based filtration methods such as ultrafiltration (UF) encompass application in broad spectra of protein sources. More importantly, selective enrichment by UF is of immense interest due to the presence of antinutrients that may dominate their perspicuous bioactivities. UF process is primarily obstructed by concentration polarization and fouling; in turn, a trade-off between productivity and selectivity emerges, especially when pure isolates are an ultimate goal. Several factors such as operating conditions and membrane equipment could leverage those pervasive contributions; therefore, UF protocols should be optimized for each unique protein mixture and mode of configuration. For instance, employing charged UF membranes or combining UF membranes with electrodialysis enables efficient separation of proteins with a similar molecular weight, which is hard to achieve by the conventional UF membrane. Meanwhile, some proposed strategies, such as utilizing ultrasonic waves, tuning operating conditions, and modifying membrane surfaces, can effectively mitigate fouling issues. A plethora of advancements in UF, from their membrane material modification to the arrangement of new configurations, contribute to the quest to actualize promising potentials of protein separation by UF, and they are reviewed in this paper. bioactivity; concentration polarization; fouling; surface modification +
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they should be separated from cognate proteins [4,5]; membrane filtration methods play a paramount role for their high throughput compared to other separation processes. Methods of separation of proteins using extraction, precipitation, centrifugation, and chromatography are common in practice, but hindered in several ways, such as by denaturation and proteolysis (of extraction and precipitation) [6, 7, 8], resolution challenges of centrifugation [9], and low yield of chromatography-based techniques [10]. Beneficially, membrane technology offers mild filtration conditions (low temperature and pressure) without phase change, retaining bioactivity [11]. Furthermore, these membrane filtration methods also possess interesting features such as molecular separation, high separation efficiency, lower footprint, less chemical consumption, and easy scale-up, which promote their application in various fields [12, 13, 14, 15]. Applications of membrane filtration in protein separation and concentration are omnipresent either in bench-scale production or industries. Various membrane applications to isolate specific peptides with particular functions are given in Tables 1-3. Initially, conventional use of pressure-driven membrane-based processes is adapted to separate molecules with different size; microfiltration (MF), for example, is carried out to remove cell debris of fermentation media or hydrolyses with a molecular size of about 0.1-10 \(\upmu\)m. Conventional ultrafiltration (UF) is also size-based and exerts low-resolution requirement owing to strict rule-of-thumb to only separate molecules with tenfold differences [16,17]. Therefore, multitudes of experimental works, which have been integrated into commercial processes, are initiated to advance UF with a combined driving force (electrical and/or concentration). These do not depend only on pressure gradients. For example, fractionation and/or purification of proteins in the range of 0.1-5 \(\upmu\)m could be fractionated by charged UF, peptides around 1-10 \(\upmu\)m by membrane chromatography, and that with 0.1-5 nm in size may be gathered by ultrasound (US)-assisted UF, high-performance tangential flow filtration (HPTFF), electro-UF membrane (EUF), electrodialysis with UF membrane (EDUF), and electrodialysis with bipolar membrane (EDBM) [18,19].