HP internalization has allowed for the use of OTX2, ENGRAILED1 (EN1), and ENGRAILED2 (EN2; collectively ENGRAILED), as therapeutic proteins in animal models of Parkinson’s disease (ENGRAILED) and glaucoma (OTX2; Sonnier et al., 2007; Alvarez-Fischer et al., 2011; Torero-Ibad et al., 2011; Thomasson et al., 2019). Here, EN1 is linked to Parkinson disease.