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The insulin-receptor substrate family plays important roles in cellular growth, signaling and survival. IRS5/DOK4 is a new member of this family identified, which is known as docking protein 4, or downstream of tyrosine kinase-4. DOK4 might have roles in insulin and IGF-1 signaling as well. Expression of IRS5/DOK4 is regulated epigenetically via histone acetylating at its promoter. DOK4 is required at early stages in the myelination process, including the initial interaction with the axon, and is also involved in Schwann cell migration and proliferation, it also regulates GDNF-mediated neurite outgrowth during neuronal development through activation of the Rap1-ERK1/2 pathway. DOK4 may represent a novel negative regulator of T cells as other DOK family members like DOK1 and DOK2.