Transmembrane channel-like protein 8 (TMC8)

Transmembrane channel-like protein 8 (TMC8) is an integral membrane protein predicted to have 8 transmembrane domains and 3 leucine zipper motifs. It is part of the transmembrane channel-like protein family and predominantly localizes to the endoplasmic reticulum and plasma membrane of keratinocytes and epithelial cells. TMC8 forms complexes with TMC6 (EVER1) and zinc transporter ZNT1, facilitating intracellular zinc regulation. Mutations in TMC8 are causally linked to Epidermodysplasia verruciformis, a rare skin disorder characterized by abnormal susceptibility to β-type HPV infections and a high risk for cutaneous squamous cell carcinoma. Functionally, TMC8 influences host cell apoptosis (especially via TNFα signaling), cellular ion homeostasis (notably zinc), and immune system interactions with infected keratinocytes, though its precise molecular activity remains under investigation. No approved drugs currently target TMC8, but its genetic and biochemical role in skin immunity and carcinogenesis make it a protein of interest in understanding virus-host interactions and epithelial cancer susceptibility.

Other names

EVER2EVIN2Epidermodysplasia verruciformis protein 2EV2epidermodysplasia verruciformis 2

Mechanistically, TMC8 acts via: Formation of complexes with TMC6 and zinc transporter ZNT1 to regulate zinc uptake; Sequestration of TRADD, impairing pro-survival complex formation and promoting apoptosis via TNFα; Regulatory effects on transcription factors induced by cytokines and zinc.