MFSD6 (major facilitator superfamily domain containing 6) is a multipass membrane transporter that functions primarily as an entry receptor for enterovirus D68 (EV-D68). 12 The protein localizes to the plasma membrane and directly binds EV-D68 viral particles through its extracellular third loop domain, which is essential for viral cell entry. 2 While initial viral attachment to cells is primarily mediated by sialic acid interactions, MFSD6 binding is required for productive viral entry into both respiratory and neural cells. 2 The MFSD6-virus interaction interface has been characterized structurally through cryo-electron microscopy. 2 Clinically, MFSD6 is significant because EV-D68 causes severe respiratory disease and acute flaccid myelitis (AFM), a poliomyelitis-like paralytic syndrome in children. 12 The identification of MFSD6 as an entry receptor has enabled therapeutic development: engineered MFSD6 decoy receptors (MFSD6-Fc fusions) potently inhibit viral uptake and provided near-complete protection in lethal mouse models of EV-D68 infection. 123 Additionally, MFSD6 may have broader roles in cellular homeostasis, with expression levels varying during energy metabolism in neural tissues. 4