In biochemistry, the membrane topology of an transmembrane protein describes which portions of the amino-acid sequence of the protein lie within the plane of the surrounding lipid bilayer and which portions protrude into the watery environment on either side. More succinictly, the membrane topology describes which regions of the polypeptide chain span the membrane.

Because biochemists know the hydrophobicity of amino acids individually, the membrane topology of a protein (and indeed whether or not it is an integral membrane protein in the first place) often may be predicted accurately on the basis of a protein's sequence alone (which of course in turn may be predicted solely from the nucleotide sequence of a gene). Such predictions are most reliably (and so they are most often) based on the assumption that the lipid bilayer-spanning portions of a transmembrane protein will assume an alpha-helical secondary structure.

Because membrane topology is frequently the first available structural information about a protein after sequencing, integral membrane proteins are often classified or grouped according to this feature. In classifying proteins in this way, biologists look at the number of times the peptide chain is predicted to cross the membrane and may in fact name a class on this basis (e.g. "7TM receptors"). Membrane topology predictions also can be invaluable for developing antibodies, drugs or other reagents that will bind and/or affect the function of the protein.