WD repeat domain phosphoinositide-interacting protein 3 (WDR45B)

WD repeat domain phosphoinositide-interacting protein 3 (WDR45B) is a key component of the autophagy machinery. It contains seven WD40 repeats that form a β-propeller structure, serving as a scaffold for protein–protein interactions within autophagy-related multiprotein complexes. WDR45B binds phosphoinositides, mainly phosphatidylinositol 3-phosphate, and is recruited to the endoplasmic reticulum and nascent autophagosomes where it promotes autophagosome membrane elongation downstream of WIPI2. WDR45B is regulated by AMPK and TSC1/TSC2 complex during cellular starvation and interacts with RB1CC1/FIP200. It is crucial for neuronal homeostasis, and its deficiency impedes autophagosome generation, causing accumulation of damaged proteins and aggregates, particularly in neurons. Mutations in WDR45B lead to neurodevelopmental and neurodegenerative disorders, including intellectual disability and spastic quadriplegia, and also play roles in cancer progression, especially hepatocellular carcinoma.

Other names

WDR45BWDR45LWIPI3WIPI-3WD repeat-containing protein 45-likeWD repeat-containing protein 45BWDR45-like proteinWIPI49-like proteinNEDSBASWIPI3 longWD repeat protein 45-like

mTOR inhibition (restores autophagy suppressed by WDR45B knockdown). Small molecule modulation of WD-repeat scaffold domains (potential pharmacological targeting as outlined for WD-repeat family).