WDR41 (WD repeat domain 41) is a non-catalytic scaffolding component of the C9orf72-SMCR8-WDR41 complex, a multiprotein assembly with dual roles in autophagy regulation and small GTPase signaling 1. Structurally, WDR41 binds to the DENN domain of SMCR8 via its C-terminal helix without directly contacting C9orf72, enabling complex assembly and function 2. The complex functions as both a GTPase-activating protein (GAP) for RAB8A and RAB11A to promote autophagosome maturation 3, and as a negative regulator of autophagy initiation by inhibiting the ULK1/ATG1 kinase complex 1. WDR41 is essential for recruiting the C9orf72-SMCR8 complex to lysosomes in response to amino acid starvation, supporting mTORC1 signaling independently of autophagy induction 4. The complex also mediates lysosomal responses through interaction with the PQLC2 cationic amino acid transporter 5. Beyond autophagy, WDR41 exhibits tumor-suppressive functions in triple-negative breast cancer, where aberrant methylation reduces expression and promotes tumorigenesis through AKT/GSK-3β/β-catenin pathway activation 6. Notably, C9orf72 mutations causing amyotrophic lateral sclerosis and frontotemporal dementia involve dysregulation of WDR41-containing complex functions, suggesting WDR41's critical role in neurodegeneration pathogenesis 7.