Lipid-binding protein required for SHH long-range signaling by binding to the dually lipid-modified SHH (ShhNp) and by promoting ShhNp mobilization, solubilization and release from the cell membrane (PubMed:22902404, PubMed:22677548). Acts by enhancing the proteolytic processing (shedding) of the lipid-modified N- and C- terminal of ShhNp at the cell surface (PubMed:24522195). Synergizes with DISP1 to cause an increase in SHH secretion (PubMed:22902404). Probable cell surface coreceptor for VEGFR2 involved in VEGFR2-mediated angiogenesis (PubMed:27834687). Interacts with SHH via the cholesterol anchor of the dually lipid-modified SHH (ShhNp) (PubMed:22902404). Interacts with PTCH1 (PubMed:22902404). Forms homooligomers and heterooligomers with SCUBE1 and SCUBE3 (By similarity). Interacts with VEGFR2 (PubMed:27834687). Secreted and tethered at the cell surface. Expressed in adult heart, lung and testis. Expressed exclusively in the neurepithelium. The CUB domain is important for the interaction with the cholesterol-anchor of SHH. The CUB domain regulates protease recruitment and activation during SHH shedding. N-glycosylated. Mutant mice with endothelial-specific inactivation of Scube2 show normal vasculogenesis and angiogenesis during embryonic development, but impaired response to exogenous VEGF, and impaired response of the endothelium to revascularization after ischemia induced by femoral artery ligation in adult (PubMed:27834687). It is unclear how SCUBE2 binds the dilipidated SHH. According to a report, the SHH cholesterol-anchor, but not palmitate, seems to be both necessary and sufficient for SCUBE2-mediated SHH release from the cell membrane (PubMed:22902404). According to a second report, SHH palmitoylation accelerates the rate of SCUBE2-mediated release (PubMed:22677548). Cholesterol modification is sufficient for a heterologous protein to bind to SCUBE2 and to be secreted in a SCUBE2-dependent manner (PubMed:22902404).