WDR91 (WD repeat domain 91) is a Rab7 effector protein that serves as a critical regulator of endosomal trafficking and lysosomal function. The protein functions as a negative regulator of phosphatidylinositol 3-kinase (PI3K) activity associated with endosomal membranes, facilitating early-to-late endosome conversion by coupling Rab switching with PtdIns3P down-regulation 1. WDR91 interacts with active GTP-bound Rab7 through its WD40 domain and inhibits Rab7-associated PI3K activity, which is essential for proper endosome maturation and cargo delivery to lysosomes 12. The protein competes with VPS41 for Rab7 binding, thereby controlling lysosome fusion in a regulated manner 3. WDR91 is particularly crucial for neuronal development and function, as brain-specific knockout in mice causes severe developmental defects, behavioral abnormalities, and neuronal loss in cerebral and cerebellar cortices 13. Loss of WDR91 leads to accumulation of giant intermediate endosomes, impaired cargo degradation, and reduced neurite complexity 13. Recent clinical reports describe WDR91 loss-of-function variants associated with severe microcephaly, developmental delay, and neurodegeneration, establishing it as a disease gene for autosomal recessive neurodevelopmental disorders 4. The protein also plays roles in viral infection pathways and has emerged as a potential therapeutic target 56.