| Function/pathway | Key mechanistic role | Key interaction partners | Subcellular localization/microdomain | Evidence type | Quantitative/other notable data | Key citations (context IDs) and source (authors, year, DOI URL) |
|---|---|---|---|---|---|---|
| ERLIN1 identity and core complex biology | Human ERLIN1 (UniProt O75477; ER lipid raft-associated protein 1) is a ~40 kDa ER membrane SPFH/PHB-family protein that hetero-oligomerizes with ERLIN2 to form large ring/cage-like scaffolds in cholesterol-rich ER nanodomains | ERLIN2 | Endoplasmic reticulum; detergent-resistant/lipid raft-like ER membrane domains; MAMs under some conditions | Review synthesis; biochemical fractionation; structural/topology inference | ERLIN1/2 described as ~40 kDa transmembrane glycoproteins; ERLIN1 is 348 aa; complexes reported as ~1000 kDa or ~40-subunit/ring-like assemblies depending on method/model | (pqac-00000008, pqac-00000009, pqac-00000010, pqac-00000019) Manganelli et al., 2021, https://doi.org/10.3390/cells10092408; Veronese et al., 2024, https://doi.org/10.26508/lsa.202402620; Cogan et al., 2024, https://doi.org/10.1007/s00439-024-02702-0 |
| Cholesterol esterification control and secretory pathway regulation | ERLIN1/2 scaffolds bridge TMUB1-L and RNF170 at ER nanodomains, restricting cholesterol esterification, favoring ER-to-Golgi cholesterol transport, and maintaining ER/Golgi architecture and secretory trafficking | ERLIN2, TMUB1-L, RNF170, TMEM259, RNF185, FAF2, VCP, ARF1/4, SOAT1 | ER membrane nanodomains; detergent-resistant membranes; ER-Golgi contact-associated regions | CRISPR/Cas9 ERLIN1/2 double KO; MS-IP; reciprocal co-IP; AlphaFold-Multimer modeling; proteomics; DRM flotation; rescue experiments | Loss of ERLINs completely prevented TMUB1-RNF170 interaction; proteomics quantified 2,742 proteins and identified 34 significant hits; SOAT1 tended to increase in DKO (log2FC 0.40, q=0.07); ERLIN loss caused ER tubule collapse, Golgi fragmentation, lipid droplet accumulation, impaired post-Golgi trafficking and migration defects; N=4 biological replicates in key proteomics | (pqac-00000000, pqac-00000001, pqac-00000002, pqac-00000003, pqac-00000039) Veronese et al., 2024, https://doi.org/10.26508/lsa.202402620 |
| ERAD of activated IP3 receptors and Ca2+ signaling | ERLIN1/2 complex recruits or scaffolds RNF170 to promote ubiquitination and ER-associated degradation of activated IP3 receptors, thereby shaping ER Ca2+ release signaling | ERLIN2, RNF170, IP3R/IP3R1 | ER membrane lipid raft-like microdomains; MAM-associated Ca2+ signaling domains | Foundational mechanistic literature summarized in reviews and disease papers; patient-genetic interpretation | In disease-oriented synthesis, unique ERLIN1 ablation was noted to increase IP3R1 levels by ~73% in vitro; disturbed IP3R degradation is proposed to impair Ca2+ signaling relevant to long-axon vulnerability | (pqac-00000018, pqac-00000019, pqac-00000021, pqac-00000024, pqac-00000029) Cogan et al., 2024, https://doi.org/10.1007/s00439-024-02702-0; Veronese et al., 2024, https://doi.org/10.26508/lsa.202402620; Huang et al., 2021, https://doi.org/10.3390/biology10080755 |
| MAM lipid raft microdomains and autophagy initiation | ERLIN1 associates with AMBRA1 in ganglioside-rich raft-like MAM microdomains; this interaction supports starvation-induced autophagosome formation and couples ER-mitochondria membrane organization to autophagy initiation | AMBRA1, MFN2, GD3/ganglioside pathway components, BECN1 | Mitochondria-associated ER membranes (MAMs); raft-like microdomains enriched in cholesterol/gangliosides | Co-immunoprecipitation; FRET; knockdown of ERLIN1, MFN2, and GD3-synthase; autophagy assays | ERLIN1-AMBRA1 interaction increased with autophagy induction; depletion of ERLIN1 impaired nutrient-deprivation-induced autophagy; interaction depended on GD3 and MFN2 integrity | (pqac-00000005, pqac-00000006, pqac-00000007) Manganelli et al., 2021, https://doi.org/10.3390/cells10092408; Manganelli et al., 2021, https://doi.org/10.1080/15548627.2020.1834207 |
| Hereditary spastic paraplegia SPG62 / patient genetics | Biallelic ERLIN1 variants disrupt splicing or the PHB/SPFH structural region, likely destabilizing ERLIN1/2 oligomers and perturbing IP3R ERAD/Ca2+ homeostasis in motor-system disease | ERLIN2; functionally linked RNF170 and IP3R1 | ER membrane complex in neurons and other cells | Human cohort genetics; RNA-seq/RT-PCR splice validation; structural modeling | Largest reported series: 13 individuals from 6 families; early onset mean 1.8 years (range 9 months-4 years); recurrent c.430+3_430+6del in 6 individuals from 4 families; thin corpus callosum in 5/13 (~40%); gait ataxia in 6/13; aid for walking typically needed 10-15 years after onset | (pqac-00000016, pqac-00000017, pqac-00000018, pqac-00000019, pqac-00000020) Cogan et al., 2024, https://doi.org/10.1007/s00439-024-02702-0 |
| Viral infection biology (HCV host factor) | ERLIN1 is a positive host factor for efficient hepatitis C virus infection, acting after entry and primary translation to promote initiation of RNA replication and a later assembly-related step | HCV proteins/core, NS3, NS5A; lipid droplets; ERLIN2 was tested but not equivalent functionally | ER detergent-resistant membranes; cholesterol-rich ER microdomains | siRNA knockdown in Huh-7 cells; reporter replicons; pseudoparticle entry assays; infectivity titration; RT-qPCR; western blot; microscopy | ERLIN1 knockdown caused ~7-10-fold lower progeny virus production; ~2-3-fold lower intracellular HCV RNA in single-cycle infection; ~4-10-fold lower core/NS3/NS5A accumulation; ~50% lower reporter activity at 48-72 h and 30-60% of control at 96 h; no effect on entry or primary IRES translation | (pqac-00000031, pqac-00000032, pqac-00000033, pqac-00000034, pqac-00000035, pqac-00000036, pqac-00000037) Whitten-Bauer et al., 2019, https://doi.org/10.3390/cells8121555 |
| Immune-cell modulation in sepsis | ERLIN1 is transcriptionally upregulated in sepsis-associated immune contexts, especially neutrophil-related settings, suggesting ER stress/proteostasis, Ca2+ signaling, and cholesterol-homeostasis roles in innate immune activation | Functionally linked RNF170, IP3R, SREBP-SCAP-INSIG axis; cell-context associations in neutrophils/monocytes/whole blood | Whole blood leukocytes; neutrophils; monocytes; HL60 neutrophil-like cells | Transcriptome mining across public datasets; RT-qPCR in stimulated whole blood; flow cytometry in leukocyte subsets and HL60 model | Public datasets showed 3.26-5.29-fold ERLIN1 increase overall; 5.29-fold increase in healthy neutrophils exposed to septic plasma; 2.6-fold increase in LPS/PGN-stimulated whole blood (p<0.01); additional examples included 1.34-fold in S. aureus infection, 1.18-fold in ICU sepsis, and 6.12-fold in neonatal sepsis; whole-blood donor experiment n=8; HL60 MFI fold changes 2.4, 1.06, and -2.36 at 6, 12, 24 h (n=3) | (pqac-00000023, pqac-00000024, pqac-00000025, pqac-00000026, pqac-00000027, pqac-00000029) Huang et al., 2021, https://doi.org/10.3390/biology10080755 |


*Table: This table summarizes experimentally supported functions, pathways, interaction partners, localization, and disease relevance of human ERLIN1 (UniProt O75477). It highlights both foundational and recent studies, including 2024 work on ERLIN1/2 scaffolds in cholesterol homeostasis and secretory pathway regulation.*