The ephrin-B2-EphB2 axis is a recurrent driver of perivascular invasion, EMT-like programmers and angiogenesis in GBM, and perturbation of this axis produces complex, sometimes paradoxical, outcomes that reflect bidirectional and context-specific signaling (Nakada et al., 2004; Qiu et al., 2019; Krusche et al., 2016; Tu et al., 2012; Broggini et al., 2022; Bhatia et al., 2020; Chen et al., 2015). The gene discussed is EPHB2; the disease is glioblastoma.