Removal of the distal axonal fragment starts with the degradation of Nmnat, which is targeted by E3 ligases. Loss of Nmat releases sarm repression, resulting in activation of Axed, NAD+ Nucleosidases and NAD+ depletion and culminating in Wallerian degeneration. Sarm and Axed interact genetically. How Axed influences NAD+ Nucleosidase activity is not known. Distal axonal fragments must be removed to allow the growth of proximal axon stumps. Activation of DsCam, PKA and Akt and JNK signaling is required for axonal re-growth. Wnd promotes axonal re-growth by phosphorylation and enhancement of DsCam and JNK signaling. E3 ligases target Wnd to counteract axonal re-growth. Changes in the splicing machinery stabilise extant RNAs promoting axon extension after injury; Axed, Axundead; CPEB, cytoplasmic polyadenylation element binding; Dscam1, Down syndrome cell adhesion molecule 1; Hiw, Highwire; JNK, c-jun n-terminal kinase; PKA, Protein kinase A; Rtca, RNA 3′-terminal phosphate cyclase; Rtcb, RNA 2′,3′-cyclic phosphate and 5′-OH ligase; Ringer, microtubule stabilizer, Sarm, Sterile alpha/Armadillo/Toll-interleukin receptor homology domain protein; Wnd, Wallenda; Xbp1, X-box binding protein 1.