SARM1 and neurodegenerative disease: Our study identifies a central role for SARM1 in apoptosis in some cells that is mediated by SARM1 activation through caspase-3 cleavage; it provides a model for dissecting the contributions of the two modes of SARM1 activation in different cellular contexts; and it has implications for the selection of ortho- versus allosteric SARM1 inhibitors for treating neurodegenerative diseases.