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Purinergic signaling can decrease developmental SC proliferation, and promote SC differentiation. The purinergic receptors P2RY2 and P2RX7 are implicated in nerve development and in the ratio of Remak SCs to myelinating SCs in differentiated peripheral nerve. P2RY2, P2RX7, and other receptors are also implicated in peripheral neuropathies and SC tumors. In SC tumors lacking the tumor suppressor <jats:italic>NF1<\/jats:italic>, the SC pathway that suppresses SC growth through P2RY2\u2010driven \u03b2\u2010arrestin\u2010mediated AKT signaling is aberrant. SC\u2010released purinergic agonists acting through SC and\/or neuronal purinergic receptors activate pain responses. In all these settings, purinergic receptor activation can result in calcium\u2010independent and calcium\u2010dependent release of SC ATP and UDP, growth factors, and cytokines that may contribute to disease and nerve repair. 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