For vision-threatening retinitis pigmentosa (RP) and dry age related macular degeneration (dry AMD), there are no FDA approved treatments. We identified lens epithelium derived growth factor fragment (LEDGF1-326) as a novel protein therapeutic. We biosynthesized, purified, and characterized LEDGF1-326. LEDGF1-326 was produced at about 20 mg per liter of culture when expressed in E.coli system, with about 95 % purity and aggregate free homogenous population with a mean hydrodynamic diameter of 9 ± 1 nm. The free energy of unfolding of LEDGF1-326 was 3.3 ± 0.5 kcal mol-1 and melting temperature was 44.8 ± 0.2 °C. LEDGF1-326 increased human retinal pigment epithelial cell (RPE) viability from 48.3 ± 5.6 to 119.3 ± 21.1 % in the presence of P23H mutant rhodopsin mediated aggregation stress. LEDGF1-326 also increased RPE FluoSphere uptake to 140 ± 10 %. Eight weeks after single intravitreal injection in Royal College of Surgeon (RCS) rats, LEDGF1-326 increased the b-wave amplitude significantly from 9.4 ± 4.6 to 57.6 ± 8.8 μV for scotopic electroretinogram (ERG) and from 10.9 ± 5.6 to 45.8 ± 15.2 μV for photopic ERG. LEDGF1-326 significantly increased the retinal outer nuclear layer thickness from 6.34 ± 1.6 to 11.7 ± 0.7 μm. LEDGF1-326 is a potential new therapeutic agent for treating retinal degenerative diseases.