Affinage

FAIM2

Protein lifeguard 2 · UniProt Q9BWQ8

Length
316 aa
Mass
35.1 kDa
Annotated
2026-06-09
62 papers in source corpus 24 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FAIM2 (Lifeguard/NMP35/LFG) is an evolutionarily conserved multi-pass membrane protein that acts as a selective endogenous inhibitor of Fas/CD95-mediated apoptosis and a determinant of neuronal survival (PMID:10535980, PMID:17635665, PMID:21957071). Originally identified in a genetic screen as protecting cells from Fas- but not TNF-alpha-mediated death, it binds the Fas receptor without altering Fas expression, agonist binding, or FADD recruitment (PMID:10535980), and instead blocks apoptosis downstream of Fas trimerization by suppressing caspase-8 activation (PMID:21957071, PMID:26796280). It localizes predominantly to the endoplasmic reticulum and Golgi and to lipid raft microdomains, where it interacts with the anti-apoptotic proteins Bcl-XL and Bcl-2 and protects type II apoptotic cells in a Bcl-XL-dependent manner by inhibiting ER calcium release, thereby blocking cytochrome c release and downstream caspase activation (PMID:17635665, PMID:26582200). FAIM2 expression is controlled transcriptionally by the PI3K/Akt pathway acting through LEF-1/beta-catenin (PMID:16033886, PMID:20336373) and is regulated post-translationally by TRIM21-mediated degradation (PMID:26398169, PMID:35468884). Functionally, FAIM2 is neuroprotective: its loss sensitizes neurons to caspase-driven death and worsens injury in cerebral ischemia, Parkinson-model dopaminergic loss, and cerebellar Purkinje/granule cell maintenance, where it acts downstream of erythropoietin/PI3K/Akt signaling alongside the related TMBIM protein GRINA (PMID:21209208, PMID:21957071, PMID:27638043, PMID:31211943). Beyond neurons, FAIM2 supports T-cell survival during early anti-viral responses through a Fas-independent mechanism (PMID:26565411), is required for myoblast differentiation (PMID:35468884), and a 3'-UTR obesity risk variant alters its expression and biases hypothalamic neuron differentiation toward cell death (PMID:38697123).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1998 Medium

    Established FAIM2 as a nervous-system-enriched membrane protein of a conserved gene family before its function was known, defining its expression domain.

    Evidence RAP-PCR differential display, Northern blot, and in situ hybridization in adult rodent nervous tissue

    PMID:9698393

    Open questions at the time
    • No molecular function assigned at this stage
    • Homology to glutamate-binding proteins not functionally validated
  2. 1999 High

    Defined the core anti-apoptotic activity: FAIM2 protects selectively against Fas-mediated death and binds Fas without blocking the canonical DISC assembly steps, indicating a non-canonical inhibitory mechanism.

    Evidence Genetic screen plus co-immunoprecipitation and cell-based apoptosis assays with mechanistic controls (Fas expression, agonist binding, FADD recruitment)

    PMID:10535980

    Open questions at the time
    • Mechanism of caspase-8 suppression not resolved
    • Subcellular site of action undefined
  3. 2002 High

    Localized FAIM2 to postsynaptic membranes and densities, linking the survival protein to synaptic neuronal compartments.

    Evidence Immunofluorescence and immunoelectron microscopy with subcellular fractionation in adult CNS

    PMID:12414123

    Open questions at the time
    • Functional consequence of synaptic localization unknown
    • Relationship to apoptotic protection not addressed
  4. 2005 High

    Connected FAIM2 expression to PI3K/Akt survival signaling and demonstrated it is functionally required to resist FasL-induced caspase-8 cleavage in neurons.

    Evidence Reporter assays, dominant-negative/constitutively active Akt, PI3K inhibition, siRNA/antisense knockdown, and gene transfer in cerebellar granule neurons and glioma cells

    PMID:16033886

    Open questions at the time
    • Direct transcription factor downstream of Akt not yet identified
    • Biochemical target of FAIM2 unresolved
  5. 2007 High

    Showed FAIM2 acts independently of FLIP and localizes to lipid rafts, establishing it as a distinct, FLIP-independent endogenous Fas inhibitor in neurons.

    Evidence Reciprocal overexpression/siRNA, caspase activity assays, and lipid raft fractionation in cortical and cerebellar neurons

    PMID:17635665

    Open questions at the time
    • Direct partners in rafts not defined
    • Stoichiometry with Fas unknown
  6. 2010 Medium

    Identified the Akt/GSK3beta/beta-catenin/LEF-1 axis as the transcriptional route driving FAIM2 expression, mechanistically linking survival signaling to FAIM2 levels.

    Evidence LEF-1 siRNA knockdown with mRNA and Western readouts in MDA-MB-231 cells

    PMID:20336373

    Open questions at the time
    • Direct LEF-1 binding site on FAIM2 promoter not mapped
    • Single cell line
  7. 2011 High

    Provided in vivo genetic proof that FAIM2 is neuroprotective, with knockout worsening ischemic injury and cerebellar neuron loss, both rescuable and tied to caspase-8 activation.

    Evidence Faim2 knockout and shRNA-transgenic mice, MCAO and oxygen-glucose deprivation, lentiviral rescue, active caspase-8/3 immunostaining

    PMID:21209208 PMID:21957071

    Open questions at the time
    • Precise biochemical step blocking caspase-8 unresolved
    • Cell-type-specific requirements not dissected
  8. 2014 Medium

    Extended FAIM2 regulation and function beyond neuronal survival, showing ERK-dependent induction in photoreceptors, MYCN-mediated repression in neuroblastoma, and an apoptosis-independent role in cell adhesion/migration.

    Evidence ERK inhibition and siRNA in 661W cells; ChIP, siRNA, adhesion/migration/sphere assays in neuroblastoma; KO meningitis model with caspase/ERK readouts

    PMID:23029562 PMID:24335530 PMID:25188511

    Open questions at the time
    • Mechanism of adhesion/migration control independent of apoptosis unknown
    • Paradoxical neurogenesis benefit of FAIM2 loss unexplained
  9. 2015 High

    Resolved the subcellular mechanism: FAIM2 at the ER/Golgi interacts with Bcl-XL/Bcl-2 and inhibits FasL-triggered ER calcium release to block cytochrome c release, defining a type II, Bcl-XL-dependent mode of protection.

    Evidence Subcellular fractionation, reciprocal Co-IP, calcium mobilization, cytochrome c release and caspase assays in cortical neurons; shRNA in breast cancer cells; T-cell KO chimeras with Fas/caspase-8 inhibitor controls

    PMID:26565411 PMID:26582200 PMID:26796280

    Open questions at the time
    • Molecular mechanism of calcium-channel regulation unknown
    • Fas-independent T-cell survival mechanism unidentified
  10. 2015 Medium

    Identified TRIM21 as a post-translational regulator that lowers FAIM2 protein and reduces Fas-induced apoptosis, adding a degradation layer to FAIM2 control.

    Evidence Protein array screen, Co-IP, Western blot, and apoptosis assays in breast cancer cells

    PMID:26398169

    Open questions at the time
    • Direct ubiquitination of FAIM2 by TRIM21 not demonstrated
    • Single Co-IP without reciprocal validation
  11. 2018 High

    Placed FAIM2 genetically downstream of erythropoietin/PI3K/Akt neuroprotection and, with GRINA, in a shared TMBIM neuroprotective module against ischemia.

    Evidence EPO administration in Faim2 KO and GRINA/FAIM2 single/double KO mice, tMCAo, OGD, caspase-8/BAX readouts

    PMID:29315561 PMID:31211943

    Open questions at the time
    • How EPO signaling induces FAIM2 transcription mechanistically unclear
    • Functional redundancy with GRINA at the molecular level undefined
  12. 2022 High

    Demonstrated a DUX4/TRIM21/miR-3202 regulatory circuit controlling FAIM2 and established FAIM2 as required for myoblast differentiation, broadening its role to muscle.

    Evidence miR inhibitor screen, siRNA/overexpression, DUX4 and TRIM21 manipulation, differentiation and apoptosis assays with rescue

    PMID:35468884

    Open questions at the time
    • Whether differentiation role is separable from anti-apoptotic role unclear
    • Direct TRIM21 ubiquitination of FAIM2 still not shown biochemically
  13. 2024 High

    Identified new contexts and partners: alphaA-crystallin interacts with FAIM2 in retina with a phospho-dependent neuroprotective effect, and an obesity-risk 3'-UTR variant alters FAIM2 expression to bias hypothalamic neurogenesis toward cell death.

    Evidence Co-IP and phospho-mutant analysis in retinal detachment; luciferase reporter, CRISPR isogenic hESC lines, and RNA-seq during hypothalamic differentiation

    PMID:38697123 PMID:39311341

    Open questions at the time
    • Functional consequence of alphaA-crystallin interaction at molecular level unclear
    • How FAIM2 dosage controls neuron differentiation gene programs unknown
  14. 2025 Medium

    Used the C. elegans ortholog to reveal an ancient role in mitochondrial-stress-triggered calcium oscillations driving serotonergic signaling and the mitochondrial UPR, linking FAIM2/TMBIM-2 calcium control to lifespan and learning.

    Evidence C. elegans genetics, calcium imaging, serotonin release and UPRmt reporters, lifespan and overexpression assays

    PMID:40100072

    Open questions at the time
    • C. elegans ortholog, not directly demonstrated for mammalian FAIM2
    • Mechanistic link from calcium oscillation to apoptosis suppression in mammals not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • The precise biochemical mechanism by which FAIM2 suppresses caspase-8 activation and regulates ER calcium fluxes—and how its anti-apoptotic and apoptosis-independent (adhesion, differentiation, calcium-signaling) functions are molecularly distinguished—remains unresolved.
  • No structural model of FAIM2 in complex with Fas or Bcl-XL
  • No direct biochemical demonstration of FAIM2 calcium-channel modulation
  • Substrate/effector basis of the Fas-independent survival functions undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0140313 molecular sequestering activity 1
Localization
GO:0005783 endoplasmic reticulum 2 GO:0005886 plasma membrane 2 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-5357801 Programmed Cell Death 5 R-HSA-162582 Signal Transduction 3
Partners
BAXBCL2BCL2L1CRYAAFASGRINATRIM21

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 LFG (FAIM2) was identified by genetic screen as an anti-apoptotic protein that protects cells from Fas-mediated apoptosis but not TNF-alpha-mediated death. LFG binds to the Fas receptor but does not regulate Fas expression, does not interfere with agonist antibody binding to Fas, and does not inhibit FADD binding to Fas. Genetic screen, co-immunoprecipitation (LFG-Fas binding), cell-based apoptosis assays Proceedings of the National Academy of Sciences of the United States of America High 10535980
1998 NMP35 (FAIM2) protein is predominantly expressed in the adult nervous system with a neuronal expression pattern, and is strongly upregulated during postnatal development. The protein shares homology with rat glutamate-binding protein (GBP), Drosophila NMDARA1, and C. elegans genes, suggesting membership in a conserved gene family. RAP-PCR differential display, Northern blot, in situ hybridization, database comparisons Molecular and cellular neurosciences Medium 9698393
2002 NMP35/Lifeguard (FAIM2) protein localizes to dendrites and postsynaptic membranes in the adult CNS, colocalizing with the glutamate receptor GluR2 and adjacent to the presynaptic vesicle protein synaptophysin. Immunoelectron microscopy confirmed postsynaptic membrane and density localization. Immunofluorescence confocal microscopy, immunoelectron microscopy, subcellular fractionation with affinity-purified antibodies Brain research. Molecular brain research High 12414123
2005 LFG/NMP35 (FAIM2) expression in cerebellar granule neurons (CGNs) is regulated by the PI3-kinase/Akt/PKB signaling pathway. Inhibition of PI3-kinase or dominant-negative Akt reduced LFG reporter activity, while constitutively active Akt increased it. Knockdown of LFG by antisense oligonucleotides or siRNA sensitized CGNs to FasL-induced caspase-8 cleavage and cell death. LFG gene transfer into FasL-sensitive glioma cells conferred protection. siRNA/antisense knockdown, reporter assay, dominant-negative and constitutively active Akt constructs, pharmacological PI3-kinase inhibition, caspase-8 cleavage assay The Journal of neuroscience : the official journal of the Society for Neuroscience High 16033886
2006 Bioinformatic analysis predicts LFG (FAIM2) resides in cellular membranes including the ER and plasma membrane, with seven transmembrane spanners and a small cytoplasmic domain. The UPF0005 consensus motif is found in the C-terminus, and the structure resembles Bax Inhibitor-1 (BI-1). Bax was found to co-immunoprecipitate with LFG. Bioinformatic sequence analysis, co-immunoprecipitation (Bax-LFG interaction) International journal of molecular medicine Low 16964429
2007 Lifeguard (FAIM2) is an endogenous inhibitor of FasL-mediated neuronal death independent of FLICE inhibitory protein (FLIP). Overexpression of LFG protected cortical neurons from FasL-induced apoptosis and decreased caspase activation. siRNA knockdown sensitized cerebellar granular and cortical neurons to FasL-induced death and caspase-8 activation. LFG was detected in lipid raft microdomains where it may interact with Fas receptor. siRNA knockdown, overexpression, caspase activity assay, lipid raft fractionation Journal of neurochemistry High 17635665
2011 Faim2-deficient mice showed increased susceptibility to oxygen-glucose deprivation in primary neurons in vitro and increased caspase-associated cell death, stroke volume, and neurological impairment after cerebral ischemia in vivo. Lentiviral Faim2 gene transfer rescued these effects, demonstrating Faim2 is neuroprotective in cerebral ischemia. Faim2 knockout mouse, middle cerebral artery occlusion model, oxygen-glucose deprivation, caspase assay, lentiviral gene transfer rescue The Journal of neuroscience : the official journal of the Society for Neuroscience High 21209208
2011 LFG (FAIM2) is required for survival and maintenance of Purkinje cells and granular cells in the cerebellum. Mice with reduced LFG expression (shRNA lentiviral transgenesis) or LFG null mice showed reduced cerebellar size, decreased internal granular layer thickness, and abnormal Purkinje cell morphology with increased active caspase-8 and caspase-3. Biochemical analysis showed LFG inhibits Fas-mediated cell death by interfering with caspase-8 activation. shRNA lentiviral transgenesis, LFG knockout mice, immunostaining for active caspase-8 and caspase-3, organotypic cerebellar culture Proceedings of the National Academy of Sciences of the United States of America High 21957071
2012 Faim2 expression in 661W photoreceptor-like cells is upregulated following Fas receptor activation and is regulated by ERK signaling. Pharmacological inhibition of ERK reduced Faim2 levels and increased susceptibility to Fas-induced caspase activation and apoptosis. siRNA knockdown of Faim2 resulted in earlier and more robust caspase activation and increased cell death after Fas antibody treatment. Pharmacological ERK pathway inhibition, siRNA knockdown, Fas-activating antibody treatment, caspase activity assay, Western blot PloS one Medium 23029562
2015 Lifeguard (FAIM2) localizes primarily to the endoplasmic reticulum and Golgi apparatus in murine cortical neurons (confirmed by subcellular fractionation). LFG interacts with Bcl-XL and Bcl-2 (but not Bax or Bak) by co-immunoprecipitation, likely at the ER. LFG protects only type II apoptotic cells from FasL-induced death in a Bcl-XL-dependent manner. LFG inhibits calcium release from the ER following FasL stimulation, which correlates with blockage of cytochrome c release and caspase activation. Subcellular fractionation, co-immunoprecipitation, calcium mobilization assay, cytochrome c release assay, caspase assay, overexpression and siRNA experiments The Journal of biological chemistry High 26582200
2015 Lifeguard (FAIM2) inhibits Fas-mediated apoptosis downstream of Fas trimerization by inhibiting caspase-8 activation in triple-negative breast cancer (MDA-MB-231) cells. Knockdown of Lifeguard via shRNA increased cisplatin efficacy, increased caspase-8 activity, and increased sensitivity to FasL-mediated cell death. shRNA knockdown, caspase-8 activity assay, cell viability assay, FasL treatment Biomedicine & pharmacotherapy Medium 26796280
2015 TRIM21 negatively modulates LFG (FAIM2) at the protein level in MDA-MB-231 breast cancer cells. TRIM21-LFG interaction was demonstrated by co-immunoprecipitation. Addition of TRIM21 decreased LFG protein levels and was associated with decreased Fas-induced apoptosis. Protein array screen, co-immunoprecipitation, Western blot, RT-PCR, flow cytometry apoptosis assay International journal of oncology Medium 26398169
2010 LFG (FAIM2) expression is regulated by the Akt/LEF-1 transcriptional pathway in breast cancer cells. GSK3β inhibition stabilizes β-catenin which associates with LEF-1 to drive LFG transcription. siRNA knockdown of LEF-1 reduced LFG mRNA levels in MDA-MB-231 cells. siRNA knockdown of LEF-1, Western blot, RT-PCR Apoptosis : an international journal on programmed cell death Medium 20336373
2014 MYCN directly represses LFG (FAIM2) expression at the transcriptional level in neuroblastoma. LFG repression in neuroblastoma cells reduced cell adhesion, increased sphere growth, and enhanced migration, conferring higher metastatic capacity, independent of its anti-apoptotic function. Expression analysis in human NBL datasets, ChIP (MYCN binding), siRNA knockdown, cell adhesion and migration assays, sphere formation assay Cell death & disease Medium 25188511
2016 Faim2-deficient mice showed significantly increased loss of dopaminergic neurons and fibers in the MPTP model of Parkinson disease compared to controls. Faim2 expression in mouse midbrain was decreased after MPTP administration, suggesting Fas-induced apoptosis contributes to dopaminergic cell death. Faim2 knockout mouse, MPTP administration, stereological counting of dopaminergic neurons, dopaminergic fiber density measurement, qRT-PCR Journal of neurochemistry Medium 27638043
2018 Faim2 upregulation contributes to the neuroprotective effects of low-dose erythropoietin (EPO) in transient brain ischemia. Low-dose EPO increased Faim2 expression and reduced stroke volume in wild-type mice, but failed to significantly reduce stroke volume in Faim2-deficient mice, placing Faim2 downstream of the EPO/PI3K/Akt signaling pathway in neuroprotection. Faim2 knockout mouse, middle cerebral artery occlusion, EPO administration, qRT-PCR, infarct volume measurement Journal of neurochemistry Medium 29315561
2019 FAIM2 (TMBIM-2) and GRINA (TMBIM-3) are both neuroprotective in transient brain ischemia and are regulated by EPO. Double-deficient mice (GRINA-/-FAIM2-/-) showed the largest infarct sizes and worst neurological deficits. FAIM2 deficiency led to upregulation of cleaved-caspase 3, pro-apoptotic BAX mRNA, and caspase-8 (not caspase-9). EPO upregulated FAIM2 and GRINA mRNA in wildtype mice. GRINA/FAIM2 single and double knockout mice, tMCAo model, OGD in primary neurons, overexpression by transfection, caspase and BAX mRNA analysis Experimental neurology High 31211943
2022 FAIM2 is targeted for degradation by TRIM21, an E3 ubiquitin ligase that is itself a DUX4 target gene; DUX4 expression reduces cellular FAIM2 levels through TRIM21. Inhibition of miR-3202 (which targets FAIM2) upregulates FAIM2. FAIM2 is required for myoblast differentiation into myotubes; FAIM2 knockdown causes increased apoptosis and failure to differentiate. FAIM2 overexpression rescued DUX4-induced cell death and myogenic differentiation defects. miR inhibitor screen, siRNA knockdown of FAIM2, FAIM2 overexpression, DUX4 overexpression, TRIM21 knockdown, differentiation assay, apoptosis assay Cell death & disease High 35468884
2025 TMBIM-2 (FAIM2 ortholog in C. elegans, XBX-6/TMBIM-2) mediates neuronal mitochondrial stress-triggered spatiotemporal Ca2+ oscillations through the Ca2+ efflux pump MCA-3, facilitating serotonin release from ADF neurons and activation of the neuronal-to-intestinal mitochondrial unfolded protein response (UPRmt). TMBIM-2 overexpression counteracted age-related decline in aversive learning and extended lifespan. C. elegans genetics, calcium imaging, serotonin release assay, UPRmt reporter, lifespan assay, TMBIM-2 overexpression The Journal of cell biology Medium 40100072
2024 αA-crystallin (HSPB4) interacts with FAIM2 in the retina following retinal detachment, as demonstrated by co-immunoprecipitation. Phosphorylation of αA-crystallin at T148 is important for this interaction and for their combined neuroprotective effect on photoreceptors. FAIM2 is induced following retinal detachment. Co-immunoprecipitation (FAIM2-αA-crystallin), phospho-mutant analysis, TUNEL staining, immunohistochemistry, immunoblotting Neurology international Medium 39311341
2014 In bacterial meningitis model, Faim2 deficiency leads to increased caspase-associated hippocampal apoptotic cell death and increased ERK activation during acute infection. After antibiotic rescue, Faim2 deficiency paradoxically led to increased hippocampal neurogenesis and improved spatial learning and memory performance. Faim2 knockout mouse, Streptococcus pneumoniae subarachnoid infection, caspase immunostaining, ERK immunostaining, Morris water maze Journal of neuropathology and experimental neurology Medium 24335530
2021 FAIM2 promotes NSCLC cell proliferation, migration, and invasion and inhibits apoptosis by activating the Wnt/β-catenin signaling pathway and facilitating EMT. FAIM2 knockdown in HARA-B4 cells reduced these activities and enhanced osteocyte adhesion. In vivo, FAIM2 participated in regulating NSCLC bone metastasis. FAIM2 overexpression and siRNA knockdown, proliferation/migration/invasion assays, Wnt/β-catenin pathway analysis, EMT marker analysis, in vivo bone metastasis model Frontiers in oncology Low 34568020
2015 LFG KO T cells show increased cell death during the initial phase of anti-viral immune response (LCMV infection), resulting in decreased numbers of activated CD8 and CD4 T cells and LCMV-specific memory T cells. LFG KO and WT T cells were equally sensitive to Fas antibody Jo-2 ex vivo, and blocking extrinsic death pathways (FasL or caspase-8 inhibitors) did not rescue the LFG KO phenotype in vivo, suggesting LFG protects T cells via a Fas-independent mechanism during early immune response. LFG knockout bone marrow chimeras, LCMV infection, T cell proliferation assay, ex vivo FasL/caspase-8 inhibitor treatment, cell death assay PloS one Medium 26565411
2024 The rs7132908 obesity risk allele within the 3' UTR of FAIM2 has allele-specific cis-regulatory activity demonstrated by luciferase reporter assay. In isogenic hESC lines differentiated to hypothalamic neurons, the risk allele influenced FAIM2 expression, decreased the proportion of neurons produced, upregulated cell death gene sets, and downregulated neuron differentiation gene sets. Luciferase reporter assay, CRISPR-Cas9 homology-directed repair to generate isogenic hESC lines, RNA-seq during hypothalamic neuron differentiation, 3D genomic data Cell genomics High 38697123

Source papers

Stage 0 corpus · 62 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 p53 in survival, death and metabolic health: a lifeguard with a licence to kill. Nature reviews. Molecular cell biology 859 26122615
1999 LFG: an anti-apoptotic gene that provides protection from Fas-mediated cell death. Proceedings of the National Academy of Sciences of the United States of America 111 10535980
2017 miR-193b availability is antagonized by LncRNA-SNHG7 for FAIM2-induced tumour progression in non-small cell lung cancer. Cell proliferation 103 29131440
2009 Association between obesity and polymorphisms in SEC16B, TMEM18, GNPDA2, BDNF, FAIM2 and MC4R in a Japanese population. Journal of human genetics 103 19851340
2016 lncRNA-SNHG7 promotes the proliferation, migration and invasion and inhibits apoptosis of lung cancer cells by enhancing the FAIM2 expression. Oncology reports 88 27666964
2007 Lifeguard/neuronal membrane protein 35 regulates Fas ligand-mediated apoptosis in neurons via microdomain recruitment. Journal of neurochemistry 63 17635665
2012 Nutritional state affects the expression of the obesity-associated genes Etv5, Faim2, Fto, and Negr1. Obesity (Silver Spring, Md.) 54 22627920
2009 LFG: a candidate apoptosis regulatory gene family. Apoptosis : an international journal on programmed cell death 50 19784873
2016 LFG-500, a newly synthesized flavonoid, attenuates lipopolysaccharide-induced acute lung injury and inflammation in mice. Biochemical pharmacology 49 27206337
2005 FasL (CD95L/APO-1L) resistance of neurons mediated by phosphatidylinositol 3-kinase-Akt/protein kinase B-dependent expression of lifeguard/neuronal membrane protein 35. The Journal of neuroscience : the official journal of the Society for Neuroscience 46 16033886
2011 Fas/CD95 regulatory protein Faim2 is neuroprotective after transient brain ischemia. The Journal of neuroscience : the official journal of the Society for Neuroscience 45 21209208
1998 Neural membrane protein 35 (NMP35): a novel member of a gene family which is highly expressed in the adult nervous system. Molecular and cellular neurosciences 42 9698393
2017 LFG-500, a novel synthetic flavonoid, suppresses epithelial-mesenchymal transition in human lung adenocarcinoma cells by inhibiting NLRP3 in inflammatory microenvironment. Cancer letters 31 28461245
2014 LFG-500 inhibits the invasion of cancer cells via down-regulation of PI3K/AKT/NF-κB signaling pathway. PloS one 31 24618693
2002 Neural membrane protein 35/Lifeguard is localized at postsynaptic sites and in dendrites. Brain research. Molecular brain research 30 12414123
2021 FAIM2 Promotes Non-Small Cell Lung Cancer Cell Growth and Bone Metastasis by Activating the Wnt/β-Catenin Pathway. Frontiers in oncology 27 34568020
2015 Lifeguard inhibition of Fas-mediated apoptosis: A possible mechanism for explaining the cisplatin resistance of triple-negative breast cancer cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 25 26796280
2011 Antiapoptotic protein Lifeguard is required for survival and maintenance of Purkinje and granular cells. Proceedings of the National Academy of Sciences of the United States of America 25 21957071
2017 MiR-3202 protects smokers from chronic obstructive pulmonary disease through inhibiting FAIM2: An in vivo and in vitro study. Experimental cell research 24 29208459
2014 Common variants in BDNF, FAIM2, FTO, MC4R, NEGR1, and SH2B1 show association with obesity-related variables in Spanish Roma population. American journal of human biology : the official journal of the Human Biology Council 22 24948161
2013 LIFEGUARD proteins support plant colonization by biotrophic powdery mildew fungi. Journal of experimental botany 21 23888068
2019 EPO regulates neuroprotective Transmembrane BAX Inhibitor-1 Motif-containing (TMBIM) family members GRINA and FAIM2 after cerebral ischemia-reperfusion injury. Experimental neurology 20 31211943
2012 ERK-mediated activation of Fas apoptotic inhibitory molecule 2 (Faim2) prevents apoptosis of 661W cells in a model of detachment-induced photoreceptor cell death. PloS one 20 23029562
2014 Modulation of hippocampal neuroplasticity by Fas/CD95 regulatory protein 2 (Faim2) in the course of bacterial meningitis. Journal of neuropathology and experimental neurology 19 24335530
2019 LncRNA DCST1-AS1 functions as a competing endogenous RNA to regulate FAIM2 expression by sponging miR-1254 in hepatocellular carcinoma. Clinical science (London, England : 1979) 18 30617187
2018 Faim2 contributes to neuroprotection by erythropoietin in transient brain ischemia. Journal of neurochemistry 18 29315561
2015 Lifeguard Inhibits Fas Ligand-mediated Endoplasmic Reticulum-Calcium Release Mandatory for Apoptosis in Type II Apoptotic Cells. The Journal of biological chemistry 18 26582200
2017 Surveillance of Dutch Patients With Li-Fraumeni Syndrome: The LiFe-Guard Study. JAMA oncology 17 28772294
2024 Variant-to-function analysis of the childhood obesity chr12q13 locus implicates rs7132908 as a causal variant within the 3' UTR of FAIM2. Cell genomics 16 38697123
2021 Targeting the ILK/YAP axis by LFG-500 blocks epithelial-mesenchymal transition and metastasis. Acta pharmacologica Sinica 16 33879841
2006 Sequence analysis shows that Lifeguard belongs to a new evolutionarily conserved cytoprotective family. International journal of molecular medicine 16 16964429
2016 Mice lacking Faim2 show increased cell death in the MPTP mouse model of Parkinson disease. Journal of neurochemistry 15 27638043
2014 MYCN repression of Lifeguard/FAIM2 enhances neuroblastoma aggressiveness. Cell death & disease 15 25188511
2010 The anti-apoptotic protein lifeguard is expressed in breast cancer cells and tissues. Cellular & molecular biology letters 15 20336406
2020 Inhibition of miR-193a-3p protects human umbilical vein endothelial cells against intermittent hypoxia-induced endothelial injury by targeting FAIM2. Aging 14 32003752
2020 Analysis of Polymorphisms rs7093069-IL-2RA, rs7138803-FAIM2, and rs1748033-PADI4 in the Group of Adolescents With Autoimmune Thyroid Diseases. Frontiers in endocrinology 13 33193078
2018 New insights into the phylogeny of the TMBIM superfamily across the tree of life: Comparative genomics and synteny networks reveal independent evolution of the BI and LFG families in plants. Molecular phylogenetics and evolution 13 29702215
2016 FAIM2, as a novel diagnostic maker and a potential therapeutic target for small-cell lung cancer and atypical carcinoid. Scientific reports 13 27677402
2015 Influence of lifestyle on the FAIM2 promoter methylation between obese and lean children: a cohort study. BMJ open 12 25922107
2015 TRIM21, a negative modulator of LFG in breast carcinoma MDA-MB-231 cells in vitro. International journal of oncology 12 26398169
2014 Novel association of the obesity risk-allele near Fas Apoptotic Inhibitory Molecule 2 (FAIM2) gene with heart rate and study of its effects on myocardial infarction in diabetic participants of the PREDIMED trial. Cardiovascular diabetology 11 24393375
2019 NFKB1-miR-612-FAIM2 pathway regulates tumorigenesis in neurofibromatosis type 1. In vitro cellular & developmental biology. Animal 9 31197610
2017 MiR-3202 - Promoted H5V Cell Apoptosis by Directly Targeting Fas Apoptotic Inhibitory Molecule 2 (FAIM2) in High Glucose Condition. Medical science monitor : international medical journal of experimental and clinical research 9 28228635
2010 Transactivation of lifeguard (LFG) by Akt-/LEF-1 pathway in MCF-7 and MDA-MB 231 human breast cancer cells. Apoptosis : an international journal on programmed cell death 9 20336373
2022 Antiapoptotic Protein FAIM2 is targeted by miR-3202, and DUX4 via TRIM21, leading to cell death and defective myogenesis. Cell death & disease 8 35468884
2017 LFG-500, a newly synthesized flavonoid, induces apoptosis in human ovarian carcinoma SKOV3 cells with involvement of the reactive oxygen species-mitochondria pathway. Experimental and therapeutic medicine 8 28587346
2015 KRT13, FAIM2 and CYP2W1 mRNA expression in oral squamous cell carcinoma patients with risk habits. Asian Pacific journal of cancer prevention : APJCP 8 25735388
2011 Silencing of anti-apoptotic transmembrane protein lifeguard sensitizes solid tumor cell lines MCF-7 and SW872 to perifosine-induced cell death activation. Oncology letters 8 22866097
2025 TMBIM-2 orchestrates systemic mitochondrial stress response via facilitating Ca2+ oscillations. The Journal of cell biology 6 40100072
2020 Interstitial serum albumin empowers osteosarcoma cells with FAIM2 transcription to obtain viability via dedifferentiation. In vitro cellular & developmental biology. Animal 6 31942726
2022 An aptasensing platform for detection of heat shock protein 70 kDa (HSP70) using a modified gold electrode with lady fern-like gold (LFG) nanostructure. Talanta 5 35500518
2015 Antiapoptotic Role for Lifeguard in T Cell Mediated Immune Response. PloS one 5 26565411
2024 HSPB4/CRYAA Protect Photoreceptors during Retinal Detachment in Part through FAIM2 Regulation. Neurology international 4 39311341
2014 Role of lifeguard β-isoform in the development of breast cancer. Oncology reports 4 25069766
2024 miR-127-5p regulates FAIM2-mediated cell apoptosis and participates in cerebral ischemia-reperfusion injury. Cellular and molecular biology (Noisy-le-Grand, France) 3 38430020
2021 HbLFG1, a Rubber Tree (Hevea brasiliensis) Lifeguard Protein, Can Facilitate Powdery Mildew Infection by Suppressing Plant Immunity. Phytopathology 3 34047620
2020 SNHG7 and FAIM2 are up-regulated and co-expressed in colorectal adenocarcinoma tissues. Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti 3 33685194
2016 Knockdown of the putative Lifeguard homologue CG3814 in neurons of Drosophila melanogaster. Genetics and molecular research : GMR 3 28002605
2013 Common rs7138803 variant of FAIM2 and obesity in Han Chinese. BMC cardiovascular disorders 3 23924573
2025 TMBIM-2 links neuronal mitochondrial stress to systemic adaptation via calcium signaling. The Journal of cell biology 2 40266590
2023 Variant-to-function analysis of the childhood obesity chr12q13 locus implicates rs7132908 as a causal variant within the 3' UTR of FAIM2. bioRxiv : the preprint server for biology 1 37662342
2026 The Anti-Apoptotic Protein Lifeguard Is Expressed in Osteosarcoma, Chondrosarcoma, and Soft Tissue Sarcoma. Oncology 0 41632739

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