DAPL1 (Death Associated Protein Like 1) functions as a multifaceted regulator of cellular homeostasis with diverse roles across different tissue types. In the retinal pigment epithelium (RPE), DAPL1 serves as a critical suppressor of cell proliferation by upregulating CDKN1A protein levels, maintaining RPE as a functional monolayer 1. DAPL1 deficiency leads to RPE overgrowth and age-related macular degeneration (AMD)-like pathological features 1. The protein operates through multiple mechanisms: it directly binds transcription factor E2F4 to inhibit MYC expression, subsequently upregulating MITF and its downstream targets NRF2 and PGC1α to enhance antioxidant defenses 2. DAPL1 also prevents epithelial-mesenchymal transition by regulating the TGF-β/MITF pathway 3 and inhibits formation of mitochondria-associated endoplasmic reticulum membranes by downregulating GRP75, thereby preventing mitochondrial calcium overload and PANoptosis 4. In immune regulation, DAPL1 controls NFATc2 activation in CD8+ T cells, with deficiency promoting antitumor immunity by preventing T cell exhaustion 5. DAPL1 also functions as a tumor suppressor in melanoma by stabilizing P21 protein 6 and regulates lipid metabolism through activation by Np63 and GRα transcription factors 7. Clinical significance includes associations with AMD susceptibility and improved survival in lung cancer patients with EGFR Del19 mutations when hypomethylated 8.