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Review
. 2025 Mar 28:13:1564649.
doi: 10.3389/fcell.2025.1564649. eCollection 2025.

Unveiling the impact of ERAP1 and ERAP2 on migration, angiogenesis and ER stress response

Irma Saulle  1   2 , Alessandra Velia Vitalyos  1 , Daniel D'Agate  1 , Mario Clerici  2   3 , Mara Biasin  1
Affiliations
Review

Unveiling the impact of ERAP1 and ERAP2 on migration, angiogenesis and ER stress response

Irma Saulle et al. Front Cell Dev Biol. .

Abstract

Recent studies have investigated the key roles exerted by ERAP1 and ERAP2 in maintaining cellular homeostasis, emphasizing their functions beyond traditional antigen processing and presentation. In particular, genetic variants of these IFNγ-inducible aminopeptidases significantly impact critical cellular pathways, including migration, angiogenesis, and autophagy, which are essential in immune responses and disease processes. ERAP1's influence on endothelial cell migration and VEGF-driven angiogenesis, along with ERAP2's role in managing stress-induced autophagy via the UPR, highlights their importance in cellular adaptation to stress and disease outcomes, including autoimmune diseases, cancer progression, and infections. By presenting recent insights into ERAP1 and ERAP2 functions, this review underscores their potential as therapeutic targets in immune regulation and cellular stress-response pathways.

Keywords: ER stress; ERAPs; autopaghy; cell biology; cell migration.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

FIGURE 1
FIGURE 1
Human diseases correlated to variants and dysregulation of ERAP1 and ERAP2. Figure created with BioRender.com.
FIGURE 2
FIGURE 2
Schematic representation illustrating the multifaceted roles of ERAP1 and ERAP2 in cellular migration, angiogenesis, and metastasis formation. AngII: angiotensin II; βTrCP: F-box/WD repeat-containing protein 1A; E1: ERAP1; E2: ERAP2; FAK: focal adhesion kinase; OSCC: oral cavity squamous cell carcinoma; PDK1: pyruvate dehydrogenase kinase 1; RhoA: Ras homolog family member A; VEGF: vascular endothelial growth factor; S6K: S6 kinase; Figure created with BioRender.com.
FIGURE 3
FIGURE 3
Schematic representation summarizing the role of ERAPs in the unfolded protein response (UPR) and autophagy. E1, ERAP1; E2, ERAP2; ER, endoplasmic reticulum; HLA-B27, human leucocyte antigen-B27; FHC, free heavy chain; IRE-1a, serine/threonine-protein kinase/endoribonuclease inositol-requiring enzyme 1 α; PSC, pancreatic stellate cell; PDAC, pancreatic ductal adenocarcinoma; UPR, unfolded protein response. Figure created with BioRender.com.
See this image and copyright information in PMC

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