WDR81 encodes a BEACH and WD40 repeat-containing protein that functions as a critical regulator of multiple cellular processes essential for neuronal health and development. The protein serves as a negative regulator of PI3 kinase activity associated with endosomal membranes, modulating phosphatidylinositol 3-phosphate content to control endosome fusion, recycling, and cargo transport from early to late endosomes 1. WDR81 plays a crucial role in aggrephagy, the autophagic clearance of ubiquitinated protein aggregates, by coordinating p62 cargo receptor function with LC3C recruitment through canonical LC3-interacting regions in its BEACH domain 1. Loss of WDR81 function leads to accumulation of protein aggregates and p62 bodies in cortical and striatal neurons 12. The protein also regulates endosomal trafficking of EGFR, affecting MAP kinase pathway activation and neural progenitor cell proliferation 3. WDR81 mutations cause severe neurodevelopmental disorders including cerebellar ataxia, intellectual disability, and microcephaly, with patient fibroblasts showing increased mitotic index and delayed mitotic progression 4. Reduced WDR81 levels are observed in brain tissues from patients with Huntington's, Parkinson's, and Alzheimer's diseases, suggesting broader roles in neurodegeneration 2.