Transmembrane protein 123 (TMEM123)

Transmembrane protein 123 (TMEM123), also known as Porimin, encodes a highly glycosylated type I transmembrane receptor characterized by a serine/threonine-rich extracellular domain similar to mucins[2][3][4]. TMEM123 is most notable for its function as a cell surface receptor mediating a specific form of cell death called oncosis—distinct from apoptosis—which results from loss of plasma membrane integrity[2][3][4]. Originally proposed as a "pro-oncosis receptor" in leukemia cells, TMEM123 is now recognized as highly expressed on tumor-infiltrating CD4+ and CD8+ T lymphocytes, particularly in colorectal cancer, where its presence promotes T cell clustering, migration, cytoskeletal organization, and effector function. TMEM123 expression on intratumoral CD8+ T cells correlates with improved survival, positioning it as a marker of favorable immune responses within the tumor microenvironment[1][3]. TMEM123's mechanistic actions involve signaling pathways controlling the actin cytoskeleton and cell adhesion, including interactions with WASP and Arp2/3 complexes[1]. While TMEM123 has not yet been established as a direct clinical drug target, its prominent role in immune surveillance and association with disease outcomes support ongoing investigation in oncology and immunology[1][3][4].

Other names

PoriminKCT-3PSEC0111UNQ641/PRO1271Pro-oncosis receptor inducing membrane injuryKeratinocytes-associated transmembrane protein 3PORIMINPORMIN

Anti-PORIMIN antibody crosslinking induces oncosis (oncotic cell death) via loss of membrane integrity, distinct from apoptosis[2][3][4]. Not drugged by small molecules or other therapies as of current knowledge.