WD repeat-containing protein 81 (WDR81) functions as a negative regulator of the PI3 kinase/PI3K activity associated with endosomal membranes via BECN1, a core subunit of the PI3K complex. By modifying the phosphatidylinositol 3-phosphate content of endosomal membranes, it regulates endosome fusion, recycling, sorting, and early to late endosome transport []. It is required for the delivery of cargos like BST2/tetherin from the early to late endosome, thereby participating indirectly in their degradation by the lysosome []. WDR81 also plays a role in aggrephagy, the macroautophagic degradation of ubiquitinated protein aggregates, by regulating the interaction of SQSTM1 with ubiquitinated proteins and recruiting MAP1LC3C []. Furthermore, it is involved in the maintenance of normal mitochondrial structure and organisation []. The protein typically contains a BEACH domain and multiple WD40 repeats. In humans, mutations in the WDR81 gene are associated with cerebellar ataxia, impaired intellectual development, and dysequilibrium syndrome 2 (CAMRQ2) [, ], as well as congenital hydrocephalus [].
