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The protein OTX2 in the retina is necessary for the maintenance of normal physiologic processes, and may be a promising therapeutic agent for some ophthalmic diseases. In this Perspective, we first shortly introduce the organization of the retina and the importance of OTX2 expression. We then present an example of reduced OTX2 activity in the developed retina associated with structural and functional consequences. We next show that homeoproteins can have neuroprotective functions. We finally review several clear examples of OTX2 non-cell autonomous activity in the retina and the effects of diminishing or providing extracellular OTX2.