Endocytosis, which plays a key role in many different species, is the process that cells take up extracellular materials through plasma membranes. Protein transduction domains (PTDs), also called cell-penetrating peptides (CPPs), are small peptides and contain a large amount of basic amino acids. Several PTDs, including arginine-rich intracellular delivery (AID) peptides, were found to be responsible for cellular uptake of macromolecules. In our previous studies, AID peptides have been proven to either covalently transport proteins or noncovalently internalize proteins, DNAs or RNAs into animal or plant cells. The mechanisms by which PTD enter cells are still in vigorous debate. Our studies indicated that the possible mechanisms of AID peptide-mediated cellular entry might involve a combination of multiple internalization pathways, including at least macropinocytosis. Furthermore, our recent reports demonstrated for the first time that AID peptides could rapidly and efficiently deliver proteins into animal and plant cells in both covalent and noncovalent protein transductions (CNPT) synchronously. Therefore, investigations of cellular uptake mediated by AID peptides facilitate our understanding of endocytosis in more details and reveal nonclassically endocytic pathways
