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Tmem117, an oligodendrocyte-enriched regulator of NCX activity, links central nervous system myelin homeostasis to counterregulation and metabolic health.

ABSTRACT: The influence of metabolic dysfunction on myelin has been well documented, yet whether central nervous system myelin homeostasis contributes to systemic metabolic regulation remains unclear. Here we identify Tmem117, a previously uncharacterized oligodendrocyte-enriched protein, as a critical regulator of this axis. Conditional deletion of Tmem117 in mature oligodendrocytes induces ER stress, broad proteome dysregulation, and demyelination, with myelin disruption leading to sex-specific effects on counterregulatory response, glucose tolerance, and hepatic lipid accumulation. Mechanistically, we provide evidence that Tmem117 modulates the sodium-calcium exchanger NCX1. These findings uncover a reciprocal link between central nervous system myelin integrity and systemic metabolic homeostasis, and position Tmem117 as a potential target for cell-specific modulation of NCX activity.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Sevasti Gaspari

LAB HEAD: Sevasti Gaspari

PROVIDER: PXD064620 | Pride | 2026-08-07

REPOSITORIES: Pride

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			Action	DRS
	20221109_170145_Gaspari_15216_RPB_TIMS.kit	Other
	4264_11-7-2022_Gaspari_15192_DIA_140min_3ul_RB1.d.zip	Other
	4265_11-7-2022_Gaspari_15193_DIA_140min_3ul_RB2.d.zip	Other
	4266_11-7-2022_Gaspari_15194_DIA_140min_3ul_RB3.d.zip	Other
	4267_11-7-2022_Gaspari_15195_DIA_140min_3ul_RB4.d.zip	Other

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