This review discusses the properties and applications of three anionic detergents—sodium dodecyl sulfate (SDS), Sarkosyl, and sodium lauroyl glutamate (SLG)—in molecular biology research. SDS is widely used for cell lysis, protein solubilization, and the purification of SDS-resistant fibrils. However, it can denature proteins and disrupt native complexes. Sarkosyl binds to unfolded and native proteins, facilitating protein solubilization and the separation of soluble proteins from Sarkosyl-insoluble neuropathological fibrils. SLG is milder than SDS and Sarkosyl and is effective for protein refolding, though its use in molecular biology is limited. The study shows that SLG has weaker effects on native protein structure and readily dissociates from native proteins, making it suitable for cell lysis in functional proteomics due to its weak binding to native proteins. SDS, Sarkosyl, and SLG differ in their micellar structures and binding properties. SDS has a larger micellar size and stronger binding to proteins, while Sarkosyl has a smaller micellar size and weaker binding. SLG has a larger head group and is less effective at binding to proteins. These differences affect their ability to solubilize and refold proteins. SDS is effective in denaturing proteins and disrupting molecular interactions, while Sarkosyl and SLG are less denaturing and can preserve native structures. The study also examines the effects of these detergents on protein refolding. Sarkosyl and SLG can be used to refold proteins, with SLG showing weaker effects on native protein structure. The binding of these detergents to proteins varies, with SDS having the strongest binding. The study highlights the importance of detergent choice in protein purification and refolding, as different detergents can affect the solubility, refolding, and functional properties of proteins. In the context of neuropathological protein fibrils, Sarkosyl and SDS are used to solubilize and characterize fibrils, while SLG is effective in refolding proteins. The study also discusses the use of these detergents in cell lysis, with SLG showing better preservation of corneal transparency and extracellular matrix components compared to SDS and other detergents. The ability of these detergents to bind to and dissociate from proteins is crucial for their application in molecular biology research, particularly in the study of protein aggregates and their characterization. The review concludes that while SDS is widely used, Sarkosyl and SLG offer alternative options for protein refolding and the study of protein aggregates, with SLG being particularly effective in preserving native protein structures.This review discusses the properties and applications of three anionic detergents—sodium dodecyl sulfate (SDS), Sarkosyl, and sodium lauroyl glutamate (SLG)—in molecular biology research. SDS is widely used for cell lysis, protein solubilization, and the purification of SDS-resistant fibrils. However, it can denature proteins and disrupt native complexes. Sarkosyl binds to unfolded and native proteins, facilitating protein solubilization and the separation of soluble proteins from Sarkosyl-insoluble neuropathological fibrils. SLG is milder than SDS and Sarkosyl and is effective for protein refolding, though its use in molecular biology is limited. The study shows that SLG has weaker effects on native protein structure and readily dissociates from native proteins, making it suitable for cell lysis in functional proteomics due to its weak binding to native proteins. SDS, Sarkosyl, and SLG differ in their micellar structures and binding properties. SDS has a larger micellar size and stronger binding to proteins, while Sarkosyl has a smaller micellar size and weaker binding. SLG has a larger head group and is less effective at binding to proteins. These differences affect their ability to solubilize and refold proteins. SDS is effective in denaturing proteins and disrupting molecular interactions, while Sarkosyl and SLG are less denaturing and can preserve native structures. The study also examines the effects of these detergents on protein refolding. Sarkosyl and SLG can be used to refold proteins, with SLG showing weaker effects on native protein structure. The binding of these detergents to proteins varies, with SDS having the strongest binding. The study highlights the importance of detergent choice in protein purification and refolding, as different detergents can affect the solubility, refolding, and functional properties of proteins. In the context of neuropathological protein fibrils, Sarkosyl and SDS are used to solubilize and characterize fibrils, while SLG is effective in refolding proteins. The study also discusses the use of these detergents in cell lysis, with SLG showing better preservation of corneal transparency and extracellular matrix components compared to SDS and other detergents. The ability of these detergents to bind to and dissociate from proteins is crucial for their application in molecular biology research, particularly in the study of protein aggregates and their characterization. The review concludes that while SDS is widely used, Sarkosyl and SLG offer alternative options for protein refolding and the study of protein aggregates, with SLG being particularly effective in preserving native protein structures.