WDR45B is a critical component of the autophagy machinery that regulates cellular degradation processes essential for neural homeostasis 1. The protein binds phosphatidylinositol 3-phosphate (PtdIns3P) and other phosphoinositides, localizing to phagophore assembly sites where it controls autophagosome elongation downstream of WIPI2 1. WDR45B functions cooperatively with its paralog WDR45, as demonstrated by more severe autophagy defects in double knockout mice compared to single knockouts 2. Mechanistically, WDR45B facilitates autophagosome-lysosome fusion by binding to the tether protein EPG5 and promoting its targeting to late endosomes/lysosomes, which is essential for proper formation of tether-SNARE fusion machinery 3. Loss of WDR45B function leads to accumulation of autophagy substrates including SQSTM1/p62 and ubiquitin-positive aggregates in brain tissues 2. Clinically, WDR45B mutations cause neurodevelopmental disorders characterized by intellectual disability, motor deficits, and learning/memory defects 24. Mouse models lacking Wdr45b exhibit swollen axons, cerebellar atrophy, and impaired neural function, establishing WDR45B as essential for maintaining neural homeostasis through proper autophagy regulation 2.