TMEM115

TMEM115 Full Name

transmembrane protein 115

TMEM115 Introduction

Transmembrane protein 115 (TMEM115), also documented in early literature as PL6, is a highly conserved, multi-pass integral membrane protein that predominantly localizes to the Golgi apparatus and the endoplasmic reticulum-Golgi intermediate compartment (ERGIC). Although its precise biochemical mechanisms are still being elucidated, extensive cellular profiling has established TMEM115 as an indispensable structural and regulatory component of the mammalian secretory pathway. Its primary physiological function is to maintain the highly organized, stacked architecture of the Golgi cisternae and to actively facilitate retrograde protein transport (vesicular traffic moving from the Golgi back to the endoplasmic reticulum). By preserving the structural integrity of this vital organelle, TMEM115 ensures the optimal microenvironment required for the flawless post-translational modification, glycosylation, and sorting of thousands of newly synthesized cellular proteins.

Figure 1. Schematic topological models of human rhomboid protease RHBDL2 and pseudoproteases iRhom2, Derlin1, UBAC2, RHBDD3 and TMEM115. (Source: Adrain C, et al. 2020)

Pathologically, the depletion or dysfunction of TMEM115 leads to severe cellular stress and profound metabolic consequences. Experimental knockdown of the TMEM115 gene causes catastrophic morphological fragmentation of the Golgi apparatus. This structural collapse directly impairs essential cellular glycosylation machineries, resulting in the production of defective, improperly modified proteins. This massive accumulation of defective proteins triggers severe organelle stress and ultimately induces cellular apoptosis. Clinically, while specific congenital mutations in TMEM115 are extremely rare, its functional disruption closely mimics the pathogenesis of Congenital Disorders of Glycosylation (CDG). Furthermore, emerging oncology research indicates that highly aggressive tumors often tightly regulate TMEM115 expression to optimize their immense secretory and metabolic demands. In these malignant contexts, manipulating TMEM115 to induce lethal Golgi fragmentation represents a novel, experimental vulnerability to trigger apoptosis specifically in rapidly dividing cancer cells.

Alternate Names for TMEM115

TMEM115; transmembrane protein 115; PL6; PP6; placental protein 6;

• 1. Ong YS, et al. TMEM115 is an integral membrane protein of the Golgi complex involved in retrograde transport. J Cell Sci. 2014 Jul 1;127(Pt 13):2825-39.
  2. Adrain C, et al. The complex life of rhomboid pseudoproteases. FEBS J. 2020 Oct;287(19):4261-4283.