DRAM2 (DNA damage regulated autophagy modulator 2) is an autophagy initiator protein primarily localized to photoreceptor inner segments, retinal pigment epithelium, and lysosomes 1. DRAM2 coordinates autophagy activation by interacting with BECN1 and UVRAG, essential autophagic machinery components, thereby enhancing phosphatidylinositol 3-kinase activity 2. This function is critical for multiple biological processes: in the retina, DRAM2 supports photoreceptor cell renewal and recycling to maintain visual function 1; in immune cells, DRAM2 mediates antimicrobial autophagy against Mycobacterium tuberculosis, with its expression inversely regulated by microRNAs MIR144* and miR-125b-5p during infection 23; and in cancer, DRAM2 expression correlates with colorectal cancer progression and represents a potential therapeutic target 4. Pathogenic biallelic DRAM2 variants cause autosomal recessive cone-rod dystrophy 21 (CORD21), characterized by photopsia, progressive outer retinal layer loss, and variable progression from cone-rod or rod-cone dystrophy patterns 15. Disease typically manifests in the third decade with central vision loss and hyperautofluorescent rings on imaging 1. Non-null variants produce milder phenotypes 1. However, DRAM2 knockout mice show no overt retinal degeneration 6, suggesting DRAM2 mutations may cause disease through dominant-negative effects rather than simple loss-of-function mechanisms.