In summary, the five TFs (CRX, NR2E1, C-MYC, LHX2, and SIX6) successfully transdifferentiated hUCMSCs into iRPE cells, which exhibited comparable properties to iPSC-RPE cells and demonstrated better therapeutic function than hUCMSCs in a rat model of AMD. Here, NR2E1 is linked to age-related macular degeneration.