Cyclin G-associated kinase (GAK; EC 2.7.11.1), also known as auxilin 2, which is highly homologous to auxilin 1, belongs to the family of Ark/Prk serine/threonine protein kinases. Like auxilin, GAK has been shown to be a cofactor for uncoating clathrin vesicles in vitro. Mechanistically, GAK binds to the α-subunit of AP-2 via sequences outside their kinase domains, while GAK also binds to the γ-subunit of AP-1 in vitro. AP-2 and AP-1 are clathrin adaptor complexes at the plasma membrane and the trans-Golgi network (TGN), respectively. A recent study also revealed that GAK regulates epidermal growth factor receptor (EGFR) signaling: Upon depletion of GAK, the expression level and the tyrosine kinase activity of EGFR increased by more than 50-fold, and its downstream signaling was also greatly altered. These results suggest that GAK may function in receptor signaling in addition to receptor trafficking[1].