In this study, we first revealed that i) Cd exposure triggered autophagic flux blockade and exacerbated AD‐like pathology; ii) SIRT5 desuccinylated and activated RAB7A at the K31 residue to rescue the Cd‐provoked AD progression by maintaining the autophagic flux; and iii) the SIRT5 levels were mainly decreased in the neurons of AD patients, which confirmed the clinical relevance of SIRT5 in AD progression. This evidence concerns the gene SIRT5 and Alzheimer disease.