Plasma membrane proteins are crucial for signal transduction, trafficking, and cell-cell interactions, all of which are vital for cell survival. These proteins, including G-protein coupled receptors, ion channels, transporters, and receptors, are key drug targets due to their central role in receiving and amplifying cellular signals. However, the isolation and purification of plasma membrane proteins pose significant challenges because of their integration with phospholipid bilayers and the small fraction of these proteins present in the plasma membrane. Biotinylation, in combination with streptavidin beads, provides an effective method for surface protein analysis by specifically labeling surface proteins without penetrating the cell membrane, enabling precise isolation and analysis with minimal contamination. In this study, we describe a 1-step method for analyzing plasma membrane proteins that can be routinely implemented in many laboratories.