TMEM135 is a transmembrane protein that serves as a crucial regulator of cellular metabolism through its effects on multiple organelles. The protein primarily functions in regulating mitochondrial dynamics by controlling the balance between mitochondrial fusion and fission, potentially through activation of DNM1L-dependent fission 1. TMEM135 also plays significant roles in peroxisomal function and lipid metabolism regulation 12. The protein affects intracellular cholesterol distribution and is essential for primary ciliogenesis, where TMEM135 depletion leads to lysosomal cholesterol accumulation and impaired Rab8 trafficking to centrioles 3. In retinal tissue, TMEM135 mutations cause significant disruption of lipid metabolism, leading to increased lipid accumulation and gene expression changes similar to those observed in age-related macular degeneration 4. The protein also influences osteogenic differentiation, as TMEM135 is targeted by miR-100-5p and its silencing inhibits bone mesenchymal stromal cell differentiation 5. TMEM135 has been associated with intelligence in population studies and appears in cancer-related gene fusions 67. Overall, TMEM135 represents a critical regulator of cellular metabolism with implications for aging-related diseases, bone health, and retinal function.