Transmembrane protein 259 (TMEM259)

Transmembrane protein 259 (TMEM259, also known as membralin) is an evolutionarily conserved, multi-pass transmembrane protein primarily localized to the endoplasmic reticulum (ER) membrane[1][4]. TMEM259 is a component of the ER-associated degradation (ERAD) pathway, which is involved in the recognition and clearance of misfolded proteins in the ER to maintain protein homeostasis[2][3][4]. TMEM259 interacts with and is required for the degradation of both luminal and membrane ERAD substrates, physically associating with key ERAD components including SYVN1 and AMFR[3]. It is also predicted to regulate ER stress response and promote neuronal survival, likely by mediating the degradation of pathogenic ER substrates[1][2][4]. Dysregulation or deficiency of TMEM259 has been implicated in neurodegenerative diseases, particularly in Alzheimer’s disease, where its downregulation enhances β-amyloid pathology and synaptic deficits[3]. TMEM259/membralin exhibits alternatively spliced isoforms with tissue-specific expression, and certain variants have been noted as tumor-associated markers in ovarian and colorectal carcinoma[1]. No direct pharmacological modulators or approved therapeutics are currently known for TMEM259.

Other names

MembralinC19orf6MBRLMEMBRALINR32184_3ASBABP1aspecific BCL2 ARE-binding protein 1MGC4022

Not applicable (No drugs/therapies directly targeting TMEM259; mechanism relates to ERAD complex and protein handling)