TBK1

Gene/Protein · 1 studies in the Atlas · also known as TANK-binding kinase 1, NAK

TANK-binding kinase 1, a kinase known from innate immunity and selective autophagy. In ESP2026 (human cell lines), lysosomal stress recruits TBK1 to lysosomes through the adaptor TAX1BP1, where it phosphorylates FNIP1 at S296, inhibits FLCN and lets TFEB enter the nucleus. ULK1 can do the same job, so the two act as alternative kinases on this route.

A kinase that helps stressed lysosomes call for repair. A kinase that, when lysosomes are damaged, helps switch on the cell's lysosome-building program.

ESP2026: TBK1 or ULK1, recruited through TAX1BP1 downstream of the v-ATPase, phosphorylates FNIP1 S296 and inhibits FLCN, a nutrient-independent route to TFEB. Best known otherwise from innate immunity and selective autophagy.

TL;DR. TBK1 appears in 1 curated study in Oliver's mTOR Atlas: 1 at the molecular level (cells, biochemistry, structure). No study in people is recorded for it in the Atlas yet. It has 2 interactions in the curated pathway model.

In the pathway model

2 interactions in the curated mTOR pathway model (1 acting from TBK1, 1 acting on it). Each row is a claim with the evidence behind it; the evidence code is the kind of study, not its quality.

Interaction	Mechanism	Evidence	Studies
TBK1 inhibits FLCN / FNIP1/2 mechanism: phosphorylation · this link in full · on the map table	TBK1 tags FNIP1, which turns FLCN off and lets TFEB escape mTORC1's grip.On the stressed lysosome, TBK1 phosphorylates FNIP1 at S296. This switches the FLCN-FNIP complex off, so mTORC1 can no longer hold TFEB in the cytoplasm and TFEB moves into the nucleus. ULK1 can do the same (ULK1-FNIP1). Holds under: Human cell lines and ATP6V1B2-mutant follicular lymphoma samples (ESP2026); a nutrient-independent lysosomal-stress route. Single study, not yet replicated. A parallel input to TFEB, not a refutation of canonical TFEB control by mTORC1 (MTORC1-TFEB): it acts by removing FLCN, which mTORC1 needs in order to reach TFEB. plausible in people, not shown directly · emerging, few independent studies	M	ESP2026
TAX1BP1 recruits TBK1 mechanism: recruitment · this link in full · on the map table	TAX1BP1 brings the kinase TBK1 to the lysosome.TAX1BP1 acts as the adaptor that brings TBK1 onto stressed lysosomes, putting the kinase next to its substrate FNIP1. Holds under: One study in human cell lines (ESP2026). Full text not accessible when this link was written; the adaptor role is taken from the authors' abstract. plausible in people, not shown directly · emerging, few independent studies	M	ESP2026

Evidence at a glance

Evidence	What it means	Studies
M	Molecular — cells, biochemistry, structure	1

No direct human evidence in the Atlas for this entity yet — everything below rests on animal or molecular work.

Studies

Year	Evidence	Study
2026	M	A TBK1/ULK1 signalling axis couples lysosomal stress to TFEB activation. ESP2026 Identifies a nutrient-independent lysosomal pathway in which v-ATPase recruits TBK1/ULK1 to phosphorylate FNIP1, inhibiting the FLCN:FNIP complex and releasing TFEB for nuclear translocation; recurrent ATP6V1B2 mutations found in follicular lymphoma patients constitutively hyperactivate this axis, driving TFEB-dependent tumor proliferation.

Related entities

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Barton, O. (2026). TBK1 [Entity page]. In Oliver's mTOR Atlas [Data set]. https://mtor-atlas.org/gene/tbk1/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_gene_tbk1,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}: TBK1},
  howpublished = {Entity page in a data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/gene/tbk1/},
  doi          = {10.5281/zenodo.22059963}
}

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