HLA-G can present a more narrow variety of peptides than its classical HLA class I counterparts due to it having a more limited polymorphism.

[6] HLA-G plays a role in immune tolerance in pregnancy, being expressed in the placenta by extravillous trophoblast cells (EVT), while the classical MHC class I genes (HLA-A and HLA-B) are not.

In order to optimize pregnancy rates, there is significant evidence that a morphological scoring system is the best strategy for the selection of embryos.

[14] However, presence of soluble HLA-G might be considered as a second parameter if a choice has to be made between embryos of morphologically equal quality.

Recent studies have emerged suggesting a link between HLA-G and P. falciparum, which is one of the most dangerous malaria strains.

High levels of soluble HLA-G have been linked to higher instances of low birth weights.

There is also an effect in Toxoplasmosis infections in pregnant women, where HLA-G is upregulated to protect the fetus from inflammation.

Individuals with Visceral leishmaniasis infections also have higher levels of soluble HLA-G, which may be due to a strategy by Leishmania to evade the immune system.

[9] Monoclonal antibodies that bind to HLA-G have been used successfully against cancers as part of a strategy to inhibit immune checkpoints.

Soluble HLA-G levels are higher in the serum of people with allergic rhinitis, or hay fever.

[20] Early results showed activity in HPV-negative HNSCC and HER2-negative metastatic colorectal cancer with WT RAS/BRAF,[21] leading to an expansion of the trial.

[22] HLA-G is both an immune checkpoint and a tumor-specific antigen, making it a target for the development of CAR T-cell therapies, which have been shown to have efficacy in in vitro mouse models.

[23] The company Invectys developed the CAR T-cell therapy IVS-3001 targeting HLA-G and began Phase1\2a clinical trials June 2023.

[24] Based on preliminary results, IVS-3001 was granted FDA fast track designation, expediting development and review of the therapy for potential use in patients with renal cell carcinoma (RCC).