This study reveals that the transcription factors LHX2 and OTX2 function together in a transcriptional module containing LDB1 and SWI/SNF to regulate the retinal pigmented epithelium differentiation program; a causal regulatory risk SNP contributes to age-related macular degeneration by altering the binding of LHX2-OTX2 to the TRPM1 promoter. The gene discussed is OTX2; the disease is age-related macular degeneration.