SARM1 is the executioner of axonal degeneration through its NMN hydrolase activity, and pharmacologic inhibition completely blocks Wallerian degeneration in acute injury models. Tool compounds (D-77, NVG-298) demonstrate in vivo efficacy in CIPN models, and Disarm Therapeutics has a Phase 1 program. The primary translational challenge is that ALS involves chronic multi-system failure rather than acute axotomy; SOD1 mouse models show only modest benefits from SARM1 deletion. Pursuing CIPN as an initial indication de-risks before ALS expansion.