Neuropilin-2 (NRP2) (NRP2)

Neuropilin-2 (NRP2) is a cell surface receptor that serves as the primary mediator of the "Resokine pathway," an evolutionarily ancient system for maintaining immune homeostasis discovered by aTyr Pharma [1, 3, 10]. Originally identified for its role in axon guidance and angiogenesis, NRP2 is highly expressed on myeloid cells, such as macrophages and dendritic cells, particularly at sites of active inflammation and within sarcoidosis granulomas [5, 6, 12]. The pathway is activated by extracellular fragments of Histidyl-tRNA synthetase (HARS), known as "Resokines," which bind to NRP2 to dampen the production of pro-inflammatory cytokines like TNF-alpha and IL-6 [8, 9, 13]. In diseases like pulmonary sarcoidosis and interstitial lung disease (ILD), the Resokine pathway is often disrupted or insufficient, leading to chronic, tissue-damaging inflammation [2, 7, 11]. Therapeutic interventions like Efzofitimod (ATYR1923) act as selective NRP2 modulators to restore homeostatic signaling and quiesce overactive myeloid cells, while other programs explore inhibiting the pathway to enhance anti-tumor immune responses in oncology [1, 5, 10].

Other names

VEGF165R2NPN2NP2Neuropilin 2NRP-2N-terminal domain of histidyl-tRNA synthetase receptor

Selective modulation of the Neuropilin-2 receptor on activated myeloid cells to downregulate pro-inflammatory cytokines and resolve chronic inflammation without systemic immune suppression.