Pursuing the questions respecting whether GFAP is truly palmitoylated in vivo and how palmitoylation might affect the physiological roles of GFAP led us to uncover a pathological mechanism that hyperpalmitoylated GFAP promotes astrogliosis, and blocking of which alleviate astrogliosis and neurodegenerative pathology in INCL mouse model. This evidence concerns the gene GFAP and infantile neuronal ceroid lipofuscinosis.