WD repeat and FYVE domain-containing protein 1 (WDFY1)

WD repeat and FYVE domain-containing protein 1 (WDFY1) is a phosphatidylinositol 3-phosphate binding adaptor protein containing multiple WD-40 repeat domains and a FYVE zinc finger domain, which localizes to early endosomes via its FYVE domain. WDFY1 is a crucial mediator of innate immune signaling, specifically by bridging Toll-like receptors TLR3 and TLR4 to the TRIF (also known as TICAM1) adaptor, resulting in the activation of transcription factors IRF3 and NF-κB and the production of type I interferons and inflammatory cytokines. The protein also plays a significant role in cancer cell biology, operating downstream of Neuropilin-2 (NRP2) to regulate endocytic and autophagic trafficking. WDFY1 expression must be tightly regulated for optimal cell survival and oncogenic signaling, and it may be involved in neurodegenerative processes (e.g., Alzheimer’s disease) where it is linked to senile plaque formation and transcriptional regulation through the FAC1 repressor. Collectively, WDFY1 serves as a molecular bridge in both immune and cancer-related signaling pathways, making it a potential therapeutic target in immunological and oncogenic diseases.

Other names

FENS1FENS-1KIAA1435WDF1ZFYVE17FYVE domain-containing protein localized to endosomes 1Phosphoinositide-binding protein 1WD40- and FYVE domain-containing protein 1zinc finger FYVE domain-containing protein 17phosphoinositide-binding protein SR1

no established drug mechanisms for WDFY1; its function is relevant to TLR3/4 signaling modulation