Lysosomal biogenesis is the coordinated process by which cells generate and maintain lysosomes, the acidic organelles responsible for macromolecule degradation, nutrient sensing, and cellular homeostasis. The master regulators of lysosomal gene expression are the MiT/TFE family transcription factors, notably TFEB and TFE3. This process is orchestrated by the MiT/TFE family of transcription factors, particularly TFEB, which serves as the master regulator of lysosomal gene expression and autophagy. Stonin-2 (STON2), a clathrin-associated sorting protein best known for its role in endocytosis and synaptic vesicle recycling, has recently been implicated in cancer biology. Beyond its canonical function, emerging evidence highlights STON2 as a critical regulator of the lysosomal-mTOR axis in oral squamous cell carcinoma (OSCC), where it contributes to tumor progression by stabilizing lysosomal integrity and anchoring mTOR at the lysosomal surface. However, the molecular details of the STON2-TFEB-mTOR axis remain unresolved. Our work aims to explore the molecular link between STON2 and TFEB in regulating lysosomal biogenesis, while also investigating how enhanced lysosomal activity parallels upregulated mTOR signaling. Since lysosomal biogenesis is essential for autophagy, and STON2 appears to mediate this process, understanding its role offers therapeutic potential. So our ultimate goal is to modulate STON2-driven lysosomal biogenesis while simultaneously restraining excessive mTOR activity to restrict OSCC progression by using natural compounds.