Transmembrane protein 135 (TMEM135)

Transmembrane protein 135 (TMEM135) is a highly conserved, multi-pass membrane protein of approximately 52 kDa that localizes to both mitochondria and peroxisomes, where it serves key regulatory functions in mitochondrial fission and lipid metabolism. TMEM135 acts as a critical mediator of mitochondria–peroxisome communication, participating in energy homeostasis—notably in brown adipose tissue via regulation of thermogenic mitochondrial fission. Mechanistically, TMEM135 promotes the recruitment and activation of the fission factor Drp1 to mitochondria, influences peroxisomal DHA export, and has been implicated in processes underlying aging, metabolic disease, and retinal degeneration. Loss or mutation of TMEM135 disrupts mitochondrial morphology (favoring fusion), leads to declines in DHA and other lipid subclasses, and is associated with accelerated aging phenotypes. Due to these central roles, TMEM135 is increasingly recognized as a potential therapeutic target in metabolic, degenerative, and age-related diseases.

Other names

PMP52Peroxisomal membrane protein 52Peroxisomal protein 52FLJ22104

Not established for direct drug targeting. Hypothetically, mechanisms would involve modulation of mitochondrial fission via Drp1 pathway or peroxisome-mitochondria lipid trafficking, as interventions enhancing or mimicking TMEM135 function could modulate lipid metabolism and mitochondrial dynamics.