CLN3 mediates chloride efflux from lysosomes

Lysosomes degrade damaged organelles and macromolecules to recycle nutrient components. Lysosomal storage diseases (LSDs) are linked to mutations of genes encoding lysosomal proteins and may lead to age-related disorders, including neurodegenerative diseases. But, how lysosomal dysfunction contributes to neurodegenerative diseases is not clear yet.. 

The researchers identify CLN3 (ceroid lipofuscinosis, neuronal 3), linked to Batten disease as a conserved lysosomal protein that regulates lysosomal chloride homeostasis, pH, and protein degradation.

Transcription factor EB (TFEB) activation enhances CLN3 function, revealing the TFEB-CLN3 signaling axis as a promising therapeutic target for lysosomal storage disorders.

Curcumin analog C1 is a natural compound with anti-inflammatory properties could enhance CLN3 activity and improve lysosomal function by activating TFEB.

https://www.cell.com/neuron/fulltext/S0896-6273(25)00886-4

https://sciencemission.com/CLN3-n-chloride-efflux-n-lysosomes