The mechanistic target of rapamycin (mTOR) signaling pathway plays a fundamental role in the regulation of cellular metabolism, autophagy, and survival within the human retinal pigment epithelium (RPE), a monolayer critical for photoreceptor support and visual function. mTOR integrates environmental signals such as nutrient availability, oxidative stress, and growth factors to modulate protein synthesis, mitochondrial function, and lysosomal activity in RPE cells. Dysregulation of mTOR—particularly chronic hyperactivation of mTORC1—has been implicated in the pathogenesis of age-related macular degeneration (AMD), leading to impaired autophagic flux, accumulation of damaged organelles, increased inflammatory signaling, and deposition of lipofuscin and drusen formation. Conversely, selective mTOR inhibition has been shown to enhance autophagy, improve cellular clearance mechanisms, and protect against RPE degeneration in experimental models. Given the RPE’s central role in retinal homeostasis, precise regulation of mTOR signaling is essential for maintaining retinal integrity and represents a promising therapeutic target in degenerative retinal diseases such as diabetic retinopathy and retinitis pigmentosa. Although the retinal pigment epithelium (RPE) is anatomically considered a part of the retina, its distinct and essential physiological roles warrant a dedicated chapter for detailed discussion.