Peripheral membrane proteins are proteins that adhere only loosely to the biological membrane with which they are associated. These molecules do not span the lipid bilayer core of the membrane, but attach indirectly, typically by binding to integral membrane proteins, or by interactions with the lipid polar head. Therefore the so-called regulatory protein subunits of many ion channels and transmembrane receptors, for example, may be defined as peripheral membrane proteins. These proteins, in contrast to integral membrane proteins, tend to collect in the water-soluble fraction during protein purification.

An exception to this rule is that cells may attach an "anchor" moiety, such as the fatty-acid anchor of lipid anchored proteins, which makes the purification properties of these proteins the same as integral membrane proteins, although researchers tend not to classify them as such.