ER forms direct contact sites with the plasma membrane and various organelles in eukaryotic cells. The crosstalk between ER and other organelles, including lysosomes, was demonstrated by several studies. ER and lysosomes have divergent roles in cell metabolism; ER operates as a platform for anabolic reactions, whereas lysosomes for catabolic reactions. Our lab focuses on elucidating the functional interplay between ER and lysosomes in the context of metabolic disease. CLN6 is an ER-resident protein and its loss results in a lysosomal storage disease, variant late infantile neuronal ceroid lipofuscinosis (vLINCL). The precise role of CLN6 and how it regulates lysosome integrity remain unclear. By using organelle-specific immunoprecipitation and high-resolution MS, we can capture the abnormal changes in these organelles' content and gain some insights into inter-organelle communication.