In contrast to receptor uncoupling, endocytosis can occur through multiple pathways. GPCR endocytosis has been shown to be either dependent or independent of arrestin activity, depending on the cell type used in the experiment; however, the former is more common. Furthermore, the same receptor expressed in two distinct cell types can be endocytosed through different mechanisms due to differences in GRK and arrestin expression: either through clathrin-coated vesicles or caveolae. In general, receptor sequestration preferentially affects receptors that are both activated and phosphorylated, but the phosphorylation is not always a necessary component of endocytosis. After being sequestered, the affected receptors can either be degraded by lysosomes or reinserted into the plasma membrane, which is called receptor recycling.
Post-translational modification also affects receptor endocytosis. For example, different glycosylations on the exterior N-terminus of dopamine receptors D and D were associated with specific endocytotic pathways. Additionally, palmitoylation, which primarily mediates receptor localization within the membrane, can also affect endocytosis. It is required for the endocytosis of thyrotropin-releasing hormone and D receptors, and it is inhibitory for leutinizing hormone and vasopressin receptor 1A receptors. It has been shown to have no effect on adrenergic receptors (specifically ß and α).