TMEM59 (transmembrane protein 59) is a multifunctional autophagy regulator with critical roles in neuroinflammation and immune homeostasis. Mechanistically, TMEM59 promotes autophagy by interacting with ATG16L1 to facilitate LC3 lipidation and autophagosome formation 12. Additionally, TMEM59 modulates protein glycosylation in the Golgi apparatus and inhibits APP transport to the cell surface 3. Beyond canonical autophagy, TMEM59 regulates chaperone-mediated autophagy (CMA) by interacting with lysosomal-associated membrane protein 2A, with TMEM59 deficiency promoting CMA activity 4. In immune cells, TMEM59 controls microglial synaptic pruning through its interaction with the C1q receptor CD93, and TMEM59 deficiency impairs synapse engulfment capacity 5. Clinically, TMEM59 dysregulation is implicated in multiple neurodegenerative and developmental disorders. TMEM59 levels increase in Alzheimer's disease patient brains and tauopathy models, while TMEM59 haploinsufficiency ameliorates tau pathology and cognitive deficits 4. Conversely, TMEM59 deficiency is associated with autism spectrum disorder through impaired microglial function 5. TMEM59 haploinsufficiency may provide neuroprotection by reducing microglial activation 6. These findings suggest TMEM59 represents a therapeutic target for tauopathy and neuroinflammatory diseases.