MEGF6 (multiple EGF-like domains 6) is a plasma membrane-associated protein with scavenger receptor activity that functions as a key regulator in cancer progression, inflammatory responses, and developmental processes. In colorectal cancer, MEGF6 promotes epithelial-to-mesenchymal transition (EMT) and metastasis via the TGFβ/SMAD signaling pathway, with upregulation associated with poor survival 1. MEGF6 also contributes to oxaliplatin resistance through miR-1254 regulation, where knockdown sensitizes cells to chemotherapy 2. In hepatocellular carcinoma, MEGF6 mediates tumor-muscle interactions by suppressing skeletal muscle differentiation through the ERK1/2 signaling pathway, promoting tumor proliferation while impairing myogenesis 3. Conversely, MEGF6 demonstrates protective roles in sepsis-induced acute lung injury by reducing inflammation and oxidative damage via the CD38/SIRT1 pathway 4. MEGF6 copy number gains are associated with SAPHO syndrome, a rare chr1 inflammatory condition 5. Additionally, MEGF6 is transcriptionally regulated by TCF3 and participates in spermatogonial stem cell fate decisions 6. These pleiotropic functions suggest MEGF6 as a therapeutic target across multiple disease contexts, though its opposing roles in different tissues warrant careful investigation before clinical application.