WD repeat-containing protein 41

WDR41 is a WD repeat-containing protein that functions as a non-catalytic component of the C9orf72-SMCR8 complex, which acts as a guanine nucleotide exchange factor (GEF) regulating autophagy (UniProt: Q9HAD4). Within this complex, WDR41 facilitates the conversion of RAB8A and RAB39B to their active GTP-bound forms, promoting autophagosome maturation, while also serving as a negative regulator of autophagy initiation by inhibiting ULK1/ATG1 kinase activity (UniProt: Q9HAD4).

The protein is involved in multiple cellular pathways controlling autophagy and vesicular trafficking, critical processes for neuronal health and proteostasis. No additional disease associations are documented in UniProt for this protein.

WDR41 is downregulated in Alzheimer's disease, showing reduced abundance in post-mortem AD brain tissue compared to age-matched controls (mean log2FC −0.42; Chaparral AD proteomics). This downregulation may impair autophagy regulation and cargo clearance, potentially contributing to the accumulation of pathogenic proteins characteristic of AD pathology.