Discoidin domain receptor 1 (DDR1) is a collagen-activated receptor tyrosine kinase with important functions in organogenesis and tissue homeostasis. The autoinhibition of DDR kinase activity is released by a two-step. First, phosphorylation of JM4 (kinase-proximal segment) tyrosines likely ejects JM4 from the cleft between the kinase N- and C-lobes, resulting in low activity similar to that of an inactive kinase alone where the A-loop still blocks the active site. In the second step, phosphorylation of the A-loop frees up the active site, resulting in a fully active kinase. Interestingly, the glycosylation at the Asn211 position could help to maintain the autoinhibitory state during the trafficking of the receptor to the cell surface by imposing steric or electrostatic effects that translate into downstream conformations.