MEGF11 is a transmembrane protein with multiple EGF-like domains that serves dual roles in retinal development and cancer biology. In the retina, MEGF11 functions as a subtype-specific mediator of homotypic cell-cell repulsion, enabling mosaic spacing of horizontal cells and other retinal neurons 1. This spacing mechanism ensures even distribution of each neuronal subtype across the retina, allowing comprehensive visual field coverage 1. MEGF11 is specifically expressed in H1 horizontal cells and serves as a reliable cellular marker in tree shrew retina 2. Beyond its retinal function, MEGF11 has emerged as a significant factor in triple-negative breast cancer (TNBC) pathology. Elevated MEGF11 expression promotes tumor recurrence by upregulating chemokines and pro-inflammatory cytokines via AKT/NF-κB signaling, creating a protumoral microenvironment 3. MEGF11 overexpression also rescues TNBC cells from anoikis (detachment-induced cell death) through tumor-platelet interactions, facilitating metastatic dissemination 4. Additionally, MEGF11 DNA methylation near its locus associates with prenatal phthalate exposure in female infants 5, and genetic variants in MEGF11 show association with Hodgkin lymphoma susceptibility 6. These findings position MEGF11 as both a critical developmental regulator and a potential therapeutic target in cancer.