Porcine epidemic diarrhea virus (PEDV) causes lethal diarrhea in piglets that leads to great economic losses in East Asia. It was reported that aminopeptidase N (APN) is the receptor for transmissible gastroenteritis virus (TGEV), human coronavirus 229E (HCoV-229E) and feline coronavirus (FeCoV) which all belong to group I coronavirus including as well as PEDV. It was also confirmed previously that porcine aminopeptidase N (pAPN) can bind to PEDV, and anti-pAPN antibodies may inhibit the combination. To investigate whether pAPN is a receptor for PEDV, we transfected MDCK cells with porcine aminopeptidase (pAPN) cDNA and this enabled non-susceptible cells to support PEDV replication and serial viral propagation. Moreover, the infection was blocked by antibodies against pAPN, implies the critical role of pAPN during virus entry. In addition, immunofluorescence assays for detection of pAPN and PEDV antigens, together with neutralization assays using antibodies against pAPN, further confirmed the correlation between pAPN expression and viral replication in pAPN-transfected MDCK cells. These results indicate that pAPN is a functional receptor for PEDV.