Regulator of cell surface receptor signal transduction. Acts as a regulator of membrane proteinases such as ADAM10 and MMP14/MT1-MMP. Activates ADAM10-dependent cleavage activity of amyloid precursor protein (APP). Activates MMP14/MT1-MMP-dependent cleavage activity (By similarity). Plays a central role in retinal vascularization by regulating norrin (NDP) signal transduction. Acts in concert with norrin (NDP) to promote FZD4 multimerization and subsequent activation of FZD4, leading to promote accumulation of beta-catenin (CTNNB1) and stimulate LEF/TCF-mediated transcriptional programs. Suprisingly, it only activate the norrin (NDP)-dependent activation of FZD4, while it does not activate the Wnt-dependent activation of FZD4, suggesting the existence of a Wnt-independent signaling that also promote accumulation the beta-catenin (CTNNB1). Interacts (when palmitoylated) with ADAM10. Interacts with MMP14/MT1-MMP (By similarity). Component of a complex, at least composed of TSPAN12, FZD4 and norrin (NDP). Expressed in the neonatal retinal vasculature but not other retinal tissues. Also detected in the neonatal meningeal vasculature and in nonvascular cell types, such as the smooth muscle cells in the neonatal intestine. Palmitoylated; required for interaction with ADAM10. Mice are viable and fertile but display defects in retinal vascularization. In retinas between P5 and P12, the centrifugal outgrowth of the nerve fiber layer (NFL) vasculature is moderately delayed in retinas. At P11, vertical sprouts and plexiform layer (OPL) capillaries appear in wild-type mice, whereas both are completely absent in mutant mice. In adult mutant mice, the plexiform layer (OPL) remains avascular, confirming that the defect is not transient. The thickness of the outer nuclear layer in retinas is consistently reduced in adult mutant but not neonatal mice, indicating that neural cells are secondarily affected by the vascular defects. Belongs to the tetraspanin (TM4SF) family.