From nociception to therapy: The expanding role of TMEM proteins in pain

Published on April 13, 2026

Life Sci. 2026 Apr 10:124391. doi: 10.1016/j.lfs.2026.124391. Online ahead of print.

ABSTRACT

Chronic pain remains a pervasive and debilitating condition with few effective treatments available. Emerging evidence reveals that transmembrane (TMEM) proteins are not merely passive structural elements but dynamic regulators of nociceptive signaling. Key TMEM family members, including TMEM100, TMEM16A/F, TMEM175, TMEM97, TMEM120A/TACAN, and TMEM233, orchestrate pain transmission by modulating ion channels, inflammatory mediators, and intracellular signaling cascades across peripheral and central pathways. Decoding their structural and functional diversity reveals new opportunities to design targeted analgesics that disrupt pathological pain at its source while sparing central nervous system side effects. By harnessing the therapeutic potential of TMEM proteins, we may redefine strategies for managing chronic and treatment-resistant pain, ultimately improving outcomes for millions affected worldwide.

PMID:41967766 | DOI:10.1016/j.lfs.2026.124391

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