TREH encodes trehalase, a membrane-bound alpha-glucosidase enzyme primarily expressed in the small intestine and kidney 1. Its primary function is hydrolysis of the dietary disaccharide trehalose into glucose molecules 1. Beyond its canonical role in trehalose metabolism, trehalose itself—independent of TREH enzymatic activity—has emerged as a potent autophagy inducer with therapeutic implications. Trehalose accumulates in the endolysosomal system and triggers low-grade lysosomal stress characterized by mild pH elevation, which activates TFEB (transcription factor EB), the master regulator of autophagy-lysosomal biogenesis 2. This mechanism involves MTORC1 inactivation and promotes expression of autophagy components and lysosomal proteins 3. Importantly, trehalase-resistant trehalose analogs produce similar autophagy-promoting effects, indicating TREH enzymatic activity is not required for these therapeutic effects 3. In Drosophila, proper trehalose metabolism is critical for survival under nutritional stress 4. Regarding disease associations, TREH polymorphisms show associations with glioblastoma risk in Han Chinese populations 5, and TREH variants are linked to triglyceride levels in Hispanic/Latino populations 6. Trehalase deficiency represents a known disorder, though specific clinical details require additional literature.