ZFYVE9 (also known as SARA - Smad anchor for receptor activation) is an early endosomal protein that functions as an adaptor in TGF-β signaling by facilitating Smad2/3 recruitment to intracellular membranes 1. The protein contains a FYVE domain that enables binding to phosphatidylinositol-3-phosphate on early endosomes, positioning it to regulate receptor-mediated signaling pathways. ZFYVE9 directly interacts with Smad2 and Smad3, promoting their phosphorylation and subsequent nuclear translocation for transcriptional activation 23. However, the functional significance of ZFYVE9 in TGF-β signaling remains controversial, with some studies demonstrating that SARA knockdown does not impair Smad activation or TGF-β target gene expression 4. The protein has been implicated in various disease contexts, including its identification as a candidate gene in aortic dissection through whole exome sequencing 5 and as a target of acquired mutations in imatinib-resistant dermatofibrosarcoma protuberans 6. Additionally, ZFYVE9 is regulated by microRNA-20a and can be targeted by therapeutic compounds like parthenolide to modulate TGF-β signaling in fibrotic diseases 12.