Detecting ALDH2 activity in live cells via conditional metabolic labeling

assays and advantageous in preserving the native enzyme context. Leveraging this advantage, we developed a screening platform that identified sennoside A as a candidate ALDH2 activator, which alleviated light-induced retinal degeneration in mice. This study establishes cMLEAD as a robust and versatile platform for probing ALDH2 activity in pathophysiologically relevant contexts and facilitating therapeutic discovery. We envision the conceptual framework of cMLEAD may be adapted to other enzymes whose catalytic products feed into detectable metabolic incorporation.