Fig. 4. Phosphorylation sites in the TFEB domain structure and their regulatory role.

TFEB can be phosphorylated at multiple serine residues by upstream kinases, such as mTOR, GSK3β, ERK2, AKT, and PKCβ. Phosphorylation of TFEB by PKCβ promotes TFEB protein stabilization. Moreover, functional studies show that TFEB localization to the lysosomal membrane is important for its inhibition by mTORC1 complex-mediated phosphorylation.