SARM1 is a NAD+ hydrolase enzyme that serves as a central executor of axonal degeneration through metabolic sensing and DNA detection 1. Upon axonal injury, SARM1 is activated by elevated nicotinamide mononucleotide (NMN) to NAD+ ratios and catalyzes NAD+ cleavage into ADP-D-ribose and cyclic ADPR, triggering Wallerian degeneration—a programmed form of axonal death 12. Recently, SARM1 was identified as a double-stranded DNA sensor that activates NAD+ degradation and cell death in response to cytosolic dsDNA, revealing a broader role in stress-induced cell death 3. Clinically, SARM1 activation is implicated in chemotherapy-induced peripheral neuropathy (CIPN), where pharmacological SARM1 inhibitors and genetic knockout protected axonal structure and function in paclitaxel-treated mice 4. SARM1 also drives glioblastoma progression through tumor-induced axonal injury and neuroinflammation; SARM1 inactivation suppressed tumor advancement and extended survival 5. Additionally, SARM1 deletion mitigated hepatic sympathetic neuropathy under metabolic stress conditions 6. These findings establish SARM1 as a compelling therapeutic target for neurodegenerative diseases and cancer-related neuropathies through inhibition of its NADase activity.