Native gels are run in non-denaturing conditions so that the analytes natural or bioactive structure is maintained.  This allows the physical size of the folded or assembled complex to affect the mobility, allowing for analysis of all four levels of the biomolecular structure.  For biological samples, detergents are used only to the extent that they are necessary to lyse lipid membranes in the cell. Complexes normally remain associated and folded as they would be in the cell. One downside, however, is that complexes may not separate cleanly or predictably, as it is difficult to predict how the molecules shape and size will affect its mobility. Addressing and solving this problem is a major aim of preparative native PAGE.
Unlike denaturing methods, native gel electrophoresis does not use a charged denaturing agent. The molecules being separated (usually proteins or nucleic acids), therefore, differ not only in molecular mass and intrinsic charge, but also the cross-sectional area, and thus experience different electrophoretic forces dependent on the shape of the overall structure. For proteins, since they remain in the native state they may be visualized not only by general protein staining reagents but also by specific enzyme-linked staining.
A specific experiment example of an application of native gel electrophoresis is to check for enzymatic activity to verify the presence of the enzyme in the sample during protein purification. For example, for the protein alkaline phosphatase, the staining solution is a mixture of 4-chloro-2-2-methylbenzenediazonium salt with 3-phospho-2-naphthoic acid-2-4-dimethyl aniline in Tris buffer. This stain is commercially sold as a kit for staining gels. If the protein is present, the mechanism of the reaction takes place in the following order: it starts with the de-phosphorylation of 3-phospho-2-naphthoic acid-2-4-dimethyl aniline by alkaline phosphatase (water is needed for the reaction). The phosphate group is released and replaced by an alcohol group from water. The electrophile 4-chloro-2-2-methylbenzenediazonium (Fast Red TR Diazonium salt) displaces the alcohol group forming the final product Red Azo dye. As its name implies, this is the final visible-red product of the reaction. In undergraduate academic experimentation of protein purification, the gel is usually run next to commercial purified samples to visualize the results and conclude whether or not purification was successful.
Native gel electrophoresis is typically used in proteomics and metallomics. However, native PAGE is also used to scan genes (DNA) for unknown mutations as in single-strand conformation polymorphism.