Preclinical research shows that the tumor-promoting properties of neuropilin-2 reside predominantly on isoform NRP2b, while NRP2a has the opposite effects in non-small cell lung cancer. In mouse models, NRP2a inhibited tumor cell proliferation, while NRP2b promoted metastasis and progression. This new understanding may lead to improved therapies that specifically target NRP2b, while sparing the tumor-inhibiting functions of NRP2a.