Clathrin is a key protein involved in receptor‐mediated endocytosis (RME), which is also known as clathrin‐mediated endocytosis (CME). Ligand/receptor binding facilitates clathrin clustering and cell surface invagination. We recently found that the typical CME ligand transferrin (Tf) can be internalized into cells without the clathrin heavy chain ( CLTC ). In this study, we clarified the unknown roles of clathrin during intracellular trafficking. Microscopic observation revealed that Tf accumulates in the deeper compartments of CLTC ‐knockdown HeLa cells. A colocalization analysis with endosome/lysosome markers showed that endocytosed Tf moves to early/late endosomes and then to lysosomes in CLTC ‐knockdown cells. This suggests that clathrin contributes to the recycling and exocytosis of endocytosed molecules.