WD repeat domain phosphoinositide-interacting protein 2 (WIPI2)

WD repeat domain phosphoinositide-interacting protein 2 (WIPI2) is a cytosolic scaffolding protein containing seven WD40 repeats that assemble into a β-propeller structure. WIPI2 binds phosphatidylinositol 3-phosphate (PI(3)P) via its conserved FRRG motif and is a critical effector recruited to the nascent autophagosome in response to autophagy induction. At the phagophore, WIPI2 interacts with the ATG16L1–ATG12–ATG5 complex, enabling LC3 lipidation and autophagosome maturation. Loss or mutation of WIPI2 disrupts autophagosome formation and is implicated in developmental disorders, defective pathogen clearance, and may contribute to cancer and neurodegeneration. WIPI2 does not act as a receptor, enzyme, or ion channel, but as a key scaffold and organizer within the autophagy pathway.

Other names

WIPI2ATG18BWIPI-2Atg21CGI-50WD repeat domain phosphoinositide-interacting protein 2WD40 repeat protein interacting with phosphoinositides 2WIPI49-like protein 2IDDSSAFLJ12979FLJ14217FLJ42984DKFZP434J154DKFZp686P02188

Drugs targeting WIPI2 would theoretically act by: - Modulating autophagosome biogenesis - Enhancing or inhibiting ATG16L1–LC3 recruitment to autophagosome membranes - Inhibition by promoting WIPI2 ubiquitination and proteasomal degradation (e.g. CUL4-RING E3 ligase–mediated action during mitosis)