In the knockout mouse, there is distal loss of the primary axon to the spinal cord; the status of the collateral axon to the striatum is unknown. In addition, the ER tubules in the mutant mouse are fewer in number and longer than those seen in the wild-type mouse. The inserts illustrate the effect of REEP1 on ER membrane curvature. In wild-type mice, membrane α-helices of REEP1 (yellow) are inserted into the outer leaflet of the ER membrane, promoting curvature, with a cytosolic C-terminal microtubule-binding domain (orange). In Reep1^–/– mice, the lack of REEP1 protein results in more planar ER membranes. As a result, ER membranes appear much longer in electron micrographs of thin sections. The lack of ER membrane curvature is hypothesized to disrupt vesicular trafficking along microtubules in long corticospinal axons of motoneurons in Reep1^–/– mice, resulting in progressive retrograde axonal degeneration.